[Tuberculosis: the counterpoint of progress]. / Tuberculosis: el contrapunto del progreso.

Along history, infectious diseases have had a direct influence in the development of humanity, with tuberculosis showing a leading role. Despite this disease being the main cause of mortality among infectious diseases, it remains neglected and constitutes a serious public health problem, especially among the poorest countries in the world. Tuberculosis greatest importance goes beyond Medicine, and a holistic view of the disease allows us to comprehend the economic and social development of a nation. Despite a historically successful control program in Chile, current figures are not auspicious and force upon us the need to address this problem with a multidisciplinary approach. The medical physician is required to put again into practice the fundamental principle of Medicine, Semiology to contribute to the control of tuberculosis.

Phenotypic and Genotypic Characterization of Macrolide, Lincosamide and Streptogramin B Resistance among Clinical Methicillin-Resistant Staphylococcus aureus Isolates in Chile.

Macrolides, lincosamides, and type B streptogramins (MLSB) are important therapeutic options to treat methicillin-resistant Staphylococcus aureus (MRSA) infections; however, resistance to these antibiotics has been emerging. In Chile, data on the MLSB resistance phenotypes are scarce in both community-(CA) and hospital-acquired (HA) MRSA isolates. Antimicrobial susceptibility to MLSB was determined for sixty-eight non-repetitive isolates of each HA-(32) and CA-MRSA (36). Detection of SCCmec elements, ermA, ermB, ermC, and msrA genes was performed by PCR. The predominant clones were SCCmec I-ST5 (HA-MRSA) and type IVc-ST8 (CA-MRSA). Most of the HA-MRSA isolates (97%) showed resistance to clindamycin, erythromycin, azithromycin, and clarithromycin. Among CA-MRSA isolates, 28% were resistant to erythromycin, azithromycin, and 25% to clarithromycin. All isolates were susceptible to linezolid, vancomycin, daptomycin and trimethoprim/sulfamethoxazole, and over 97% to rifampicin. The ermA gene was amplified in 88% of HA-MRSA and 17% of CA-MRSA isolates (p < 0.001). The ermC gene was detected in 6% of HA-SARM and none of CA-SARM isolates, whereas the msrA gene was only amplified in 22% of CA-MRSA (p < 0.005). Our results demonstrate the prevalence of the cMLSB resistance phenotype in all HA-MRSA isolates in Chile, with the ermA being the predominant gene identified among these isolates.

Tuberculosis: el contrapunto del progreso / Tuberculosis: the counterpoint of progress

Resumen A lo largo de la historia, las enfermedades infecciosas han influido directamente en el desarrollo de la humanidad y en este proceso, la tuberculosis ha tenido un rol protagónico. Esta enfermedad mata más seres humanos que cualquier otra de causa infecciosa y, a pesar de esto, continúa siendo una entidad olvidada y un grave problema de salud pública, sobre todo en las naciones más pobres. La trascendencia de la tuberculosis va más allá del ámbito médico y una visión holística de ella nos permite comprender el grado de desarrollo económico y social de un Estado. Si bien Chile mantenía un programa de control históricamente exitoso, las cifras actuales no son auspiciosas y obligan a analizar el problema desde una mirada multidisciplinaria. Es en este marco que planteamos que el médico clínico, para aportar en el control de la enfermedad, debe poner nuevamente en práctica uno de los principios básicos de la Medicina: la semiología.

Abstract Along history, infectious diseases have had a direct influence in the development of humanity, with tuberculosis showing a leading role. Despite this disease being the main cause of mortality among infectious diseases, it remains neglected and constitutes a serious public health problem, especially among the poorest countries in the world. Tuberculosis greatest importance goes beyond Medicine, and a holistic view of the disease allows us to comprehend the economic and social development of a nation. Despite a historically successful control program in Chile, current figures are not auspicious and force upon us the need to address this problem with a multidisciplinary approach. The medical physician is required to put again into practice the fundamental principle of Medicine, Semiology to contribute to the control of tuberculosis.

[Carbapenemases produced by Carbapenem-resistant Pseudomonas aeruginosa isolated from hospitals in Chile]. / Carbapenemasas en aislamientos de Pseudomonas aeruginosa resistentes a carbapenémicos aisladas en hospitales de Chile.

BACKGROUND: Carbapenem resistance mediated by carbapenemases in Pseudomonas aeruginosa is an important mechanism; however, loss of porin OprD remains as the most frequent. AIM: To determine the proportion of P. aeruginosa isolates, resistant to imipenem and/or meropenem, producing carbapenemases, the type of enzyme produced and the genetic relationship between the isolates. METHODS: One hundred and thirteen resistant to at least one carbapenem isolates, obtained in 12 hospitals and 9 cities in Chile were studied. Additionally, susceptibility to ceftazidime, amikacin, gentamicin, piperacillin/tazobactam, ciprofloxacin and colistin was determined. Carba NP was performed and in the positive isolates carbapenemase genes were detected by PCR. The isolates were typified by restriction with SpeI and PFGE. RESULTS: Not all isolates produce carbapenemases, and only in 61/113 of them (54%) the blaKPC (32) or blaVIM (29) was amplified. In none of the isolates was found the coharboring of both genes. The pulsotypes indicated no clonal dissemination of the isolates, evidencing an important genetic diversity. CONCLUSIONS: P. aeruginosa isolates producing carbapenemases, obtained in Chilean hospitals carry blaKPC and blaVIM genes and, mostly, are polyclonal. These results emphasize the importance of carrying out epidemiological studies with a greater number of isolates to allow a better understanding of the epidemiology of carbapenemase-producing P. aeruginosa in Chile.

Carbapenemasas en aislamientos de Pseudomonas aeruginosa resistentes a carbapenémicos aisladas en hospitales de Chile

Resumen Introducción: La resistencia a carbapenémicos mediada por carbapenemasas en Pseudomonas aeruginosa es un mecanismo importante; sin embargo, la pérdida de la porina OprD continúa siendo el mecanismo más frecuente. Objetivo: Determinar la proporción de aislados de P. aeruginosa, resistentes a imipenem y/o meropenem, productores de carbapenemasas, el tipo de enzima producida y la relación genética entre los aislados. Material y Métodos: Se incluyó 113 aislados resistentes al menos a un carbapenémico, provenientes de 12 hospitales de 9 ciudades de Chile. Adicionalmente se determinó la susceptibilidad a ceftazidima, amikacina, gentamicina, piperacilina/tazobactam, ciprofloxacina y colistina. Se realizó Carba NP y en los aislados positivos (n: 61) se detectó genes de carbapenemasas por RPC. Los aislados fueron tipificados por restricción con SpeI y PFGE. Resultados: No todos los aislados presentan carbapenemasas, y sólo en 61/113 de ellos (54%) se amplificó blaKPC (32) o blaVIM (29). En ninguno de los aislados se encontró co-portación de ambos genes. Los pulsotipos indican que no hay diseminación clonal de los aislados, evidenciando una importante diversidad genética. Conclusiones: Los aislados de P. aeruginosa productores de carbapenemasas, obtenidos en hospitales de Chile, portan genes blaKPC y blaVIM y, en su mayoría, son policlonales. Estos resultados ponen énfasis en la importancia de realizar estudios epidemiológicos con mayor número de aislados que permitan conocer mejor la epidemiología de P. aeruginosa productoras de carbapenemasas en Chile.

Abstract Background: Carbapenem resistance mediated by carbapenemases in Pseudomonas aeruginosa is an important mechanism; however, loss of porin OprD remains as the most frequent. Aim: To determine the proportion of P. aeruginosa isolates, resistant to imipenem and/or meropenem, producing carbapenemases, the type of enzyme produced and the genetic relationship between the isolates. Methods: One hundred and thirteen resistant to at least one carbapenem isolates, obtained in 12 hospitals and 9 cities in Chile were studied. Additionally, susceptibility to ceftazidime, amikacin, gentamicin, piperacillin/tazobactam, ciprofloxacin and colistin was determined. Carba NP was performed and in the positive isolates carbapenemase genes were detected by PCR. The isolates were typified by restriction with SpeI and PFGE. Results: Not all isolates produce carbapenemases, and only in 61/113 of them (54%) the blaKPC (32) or blaVIM (29) was amplified. In none of the isolates was found the coharboring of both genes. The pulsotypes indicated no clonal dissemination of the isolates, evidencing an important genetic diversity. Conclusions: P. aeruginosa isolates producing carbapenemases, obtained in Chilean hospitals carry blaKPC and blaVIM genes and, mostly, are polyclonal. These results emphasize the importance of carrying out epidemiological studies with a greater number of isolates to allow a better understanding of the epidemiology of carbapenemase-producing P. aeruginosa in Chile.

Actividad de cobre sobre cocáceas grampositivas multi-resistentes a los antibióticos aisladas en hospitales chilenos / Copper activity against multiresistant Gram-positive cocci isolated in Chilean hospitals

Background: Nosocomial infections caused by multiresistant Gram-positive cocci are a serious problem for public health systems worldwide. The use of copper surfaces in hospital environments has proven to be an effective alternative for the control of various microorganisms, including multiresistant nosocomial pathogens. Aim: To determine the association between antibiotic multiresistance and higher levels of copper tolerance in Gram-positive cocci isolated from Chilean hospitals, which might confer a selective advantage in environments with copper. Methods: The ionic copper tolerance levels were evaluated using the Mueller Hinton agar dilution method, in S. aureus and Enterococcus spp. strains with different levels of susceptibility to clinically relevant antibiotics. Results: A statistically significant association between higher levels of tolerance to copper ion and multi-resistance to antibiotics in Enterococcus spp. was observed.

Introducción: Las infecciones nosocomiales, producidas por bacterias cocáceas grampositivas multi-resistentes constituyen un serio problema para los sistemas de salud pública mundial. El uso de superficies de cobre en ambientes hospitalarios ha demostrado ser una alternativa efectiva para el control de diversos microorganismos, incluyendo patógenos nosocomiales multi-resistentes. Objetivo: Determinar la asociación entre la multi-resis-tencia a antimicrobianos y mayores niveles de tolerancia a cobre en bacterias cocáceas grampositivas aisladas de hospitales chilenos, que podrían conferir una ventaja selectiva en ambientes cobrizados. Material y Métodos: Se evaluó los niveles de tolerancia a cobre iónico en grupos de cepas de Staphylococcus aureus y Enterococcus spp. con distintos grados de susceptibilidad a antimicrobianos de relevancia clínica, mediante el método de dilución en agar Mueller Hinton. Resultados: Se observó una asociación estadísticamente significativa entre mayores niveles de tolerancia a cobre iónico y la multi-resistencia a antimicrobianos en Enterococcus spp.

[Copper activity against multiresistant Gram-positive cocci isolated in Chilean hospitals]. / Actividad de cobre sobre cocáceas grampositivas multi-resistentes a los antibióticos aisladas en hospitales chilenos.

BACKGROUND: Nosocomial infections caused by multiresistant Gram-positive cocci are a serious problem for public health systems worldwide. The use of copper surfaces in hospital environments has proven to be an effective alternative for the control of various microorganisms, including multiresistant nosocomial pathogens. AIM: To determine the association between antibiotic multiresistance and higher levels of copper tolerance in Gram-positive cocci isolated from Chilean hospitals, which might confer a selective advantage in environments with copper. METHODS: The ionic copper tolerance levels were evaluated using the Mueller Hinton agar dilution method, in S. aureus and Enterococcus spp. strains with different levels of susceptibility to clinically relevant antibiotics. RESULTS: A statistically significant association between higher levels of tolerance to copper ion and multi-resistance to antibiotics in Enterococcus spp. was observed.

[Pharmacokinetics/pharmacodinamic (PK/PD) evaluation of a short course of oral administration of metronidazole for the management of infections caused by Bacteroides fragilis]. / Evaluación farmacocinética/farmacodinámica (PK/PD) de un esquema de administración oral de metronidazol en intervalo ampliado para el manejo de infecciones producidas por Bacteroides fragilis.

INTRODUCTION: Metronidazole is the antibiotic of choice for the management of infections caused by anaerobes. Its administration requires multiple daily doses causing increased medication errors. Due to its high post-antibiotic effect and rapid concentration-dependent bactericidal activity, administration of this antibiotic in an extended dosing interval would achieve PK/PD parameters effectively. OBJECTIVE: To assess the probability of achieving effective PK/PD relationship with the administration of 1,000 mg every 24 hours of metronidazole for Bacteroides fragilis infections. METHODS: A clinical trial was conducted in a group of volunteers who received a single oral dose of 500 or 1,000 mg of metronidazole. Determinations of values of Cmax, t max, and AUCC0-24 h. determined using the trapezoidal method, were obtained for a Markov simulation that would allow for determining the likelihood of achieving a AUC0-24 h/MIC ratio above 70 for infections caused by susceptible B. fragilis. RESULTS: Cmax (24,03 ± 6,89 mg/L) and t max (1,20 ± 0.80 hrs) and the value of AUC0-24 h (241.91 ± 48.14 mg * h/L) were determined. The probability of obtaining a AUC0-24 h/MIC ratio greater than 70 was greater than 99%. CONCLUSION: From a pharmacokinetic perspective, with the administration of a daily dose of 1,000 mg of metronidazole, it is possible to achieve a therapeutic goal of AUC0-24 h/MIC ratio above 70 for the treatment of anaerobic infections.

Evaluación farmacocinética/farmacodinámica (PK/PD) de un esquema de administración oral de metronidazol en intervalo ampliado para el manejo de infecciones producidas por Bacteroides fragilis / Pharmacokinetics/pharmacodinamic (PK/PD) evaluation of a short course of oral administration of metronidazole for the management of infections caused by Bacteroides fragilis

Introduction: Metronidazole is the antibiotic of choice for the management of infections caused by anaerobes. Its administration requires multiple daily doses causing increased medication errors. Due to its high post-antibiotic effect and rapid concentration-dependent bactericidal activity, administration of this antibiotic in an extended dosing interval would achieve PK/PD parameters effectively. Objective: To assess the probability of achieving effective PK/PD relationship with the administration of 1,000 mg every 24 hours of metronidazole for Bacteroides fragilis infections. Methods: A clinical trial was conducted in a group of volunteers who received a single oral dose of 500 or 1,000 mg of metronidazole. Determinations of values of Cmax, t max, and AUCC0-24 h. determined using the trapezoidal method, were obtained for a Markov simulation that would allow for determining the likelihood of achieving a AUC0-24 h/MIC ratio above 70 for infections caused by susceptible B. fragilis. Results: Cmax (24,03 ± 6,89 mg/L) and t max (1,20 ± 0.80 hrs) and the value of AUC0-24 h (241.91 ± 48.14 mg * h/L) were determined. The probability of obtaining a AUC0-24 h/MIC ratio greater than 70 was greater than 99%. Conclusion: From a pharmacokinetic perspective, with the administration of a daily dose of 1,000 mg of metronidazole, it is possible to achieve a therapeutic goal of AUC0-24 h/MIC ratio above 70 for the treatment of anaerobic infections.

Introducción: Metronidazol es el antimicrobiano de elección para el manejo de infecciones anaeróbicas. Su administración requiere de dosis múltiples provocando aumento en errores medicamentosos. Debido al efecto post-antibiótico y a la actividad bactericida concentración-dependiente, la administración de metronidazol en intervalos ampliados de administración permitiría alcanzar parámetros PK/PD efectivos. Objetivo: Evaluar la probabilidad de alcanzar una relación PK/PD efectiva con la administración de 1.000 mg cada 24 h de metronidazol para infecciones por Bacteroides fragilis. Método: Se realizó un ensayo clínico sobre un grupo de voluntarios a quienes se les administró una monodosis oral de 500 y 1.000 mg de metronidazol, respectivamente. Se establecieron parámetros farmacocinéticos empleando el método trapezoidal. Se realizó una simulación de Markov que permitiera establecer la probabilidad de alcanzar una relación AUC0-24 h/CIM > 70 en infecciones por B. fragilis. Resultados: Se determinaron los valores de Cmax (24,03 ± 6,89 mg/L), t max (1,20± 0,8h) y AUC0-24 h (241,91 ± 48,14 mg*h/L), con lo cual la probabilidad de alcanzar una relación AUC0-24 h/CIM > 70 con 1.000 mg de metronidazol fue superior a 99%. Conclusión: Con la administración de 1.000 mg cada 24 h sería posible alcanzar una relación PK/PD efectiva para el tratamiento de infecciones anaeróbicas.

Prevalencia del determinante de resistencia plasmídica a quinolonas aac(6’)-Ib-cren cepas de Escherichia coli y Klebsiella pneumoniae productoras de BLEE aisladas en diez hospitales de Chile / Prevalence of plasmid-mediated quinolone resistance determinant aac(6’)-Ib-cr among ESBL producing enterobacteria isolates from Chile an hospitals

Introducción: En Chile no se conoce la frecuencia del determinante plasmídico de resistencia a quinolonas(DPRQ) aac(6 )-Ib-cr en cepas de Klebsiella pneumoniae y Escherichia coli productoras de BLEE. Metodología: Utilizando PCR, RFLP y secuenciación se detectó aac(6 )-Ib y aac(6 )-Ib-cr en cepas aisladas en 10 hospitales chilenos entre 2008 y 2009.Resultados: Este DPRQ fue detectado ampliamente en K. pneumoniae (54%) y E. coli (74%). La CIM50de CIP fue mayor en cepas con aac(6’)-Ib-cr; 8 veces en K. pneumoniae y 4 en E. coli. En 13 cepas deK. pneumoniae y 3 de E. coli se encontraron ambos genes simultáneamente. Conclusión: Este es el primer informe de aac(6’)-Ib-cr en cepas de K. pneumoniae y E. coli productoras de BLEE aisladas en hospitales chilenos distribuidos en una extensión geográflca superior a 2.800 km (AU)

Introduction: The frequency of aac(6 )-Ib-cr gene in ESBL-producing strains of Klebsiella pneumoniae and Escherichia coli is unknown, in Chile. Methodology: The aac(6 )-Ib and aac(6’)-Ib-cr genes were investigated using polymerase chain reaction(PCR), restriction fragment length polymorphism (RFLP), and sequencing, in strains isolated from 10Chilean hospitals between 2008-2009.Results: The aac(6’)-Ib-cr gene was detected in 54% of K. pneumoniae and 74% of E. coli strains. The CIM50 of CIP was higher among strains harboring aac(6’)-Ib-cr, 8 times higher in K. pneumoniae and 4 times higherin E. coli. Moreover, both aac(6’)-Ib and aac(6’)-Ib-cr were simultaneously found in 13 K. pneumoniae and3 E. coli isolates. Conclusion: This is the first report of aac(6’)-Ib-cr in ESBL-producing strains of K. pneumoniae and E. coliisolated from in-patients in Chilean hospitals located along an area of more than 2,800 Km (AU)

[Prevalence of plasmid-mediated quinolone resistance determinant aac(6')-Ib-cr among ESBL producing enterobacteria isolates from Chilean hospitals]. / Prevalencia del determinante de resistencia plasmídica a quinolonas aac(6')-Ib-cr en cepas de Escherichia coli y Klebsiella pneumoniae productoras de BLEE aisladas en diez hospitales de Chile.

INTRODUCTION: The frequency of aac(6')-Ib-cr gene in ESBL-producing strains of Klebsiella pneumoniae and Escherichia coli is unknown, in Chile. METHODOLOGY: The aac(6')-Ib and aac(6')-Ib-cr genes were investigated using polymerase chain reaction (PCR), restriction fragment length polymorphism (RFLP), and sequencing, in strains isolated from 10 Chilean hospitals between 2008-2009. RESULTS: The aac(6')-Ib-cr gene was detected in 54% of K. pneumoniae and 74% of E. coli strains. The CIM(50) of CIP was higher among strains harboring aac(6')-Ib-cr, 8 times higher in K. pneumoniae and 4 times higher in E. coli. Moreover, both aac(6')-Ib and aac(6')-Ib-cr were simultaneously found in 13 K. pneumoniae and 3 E. coli isolates. CONCLUSION: This is the first report of aac(6')-Ib-cr in ESBL-producing strains of K. pneumoniae and E. coli isolated from in-patients in Chilean hospitals located along an area of more than 2,800 Km.

Aislamiento de enterococcus faecium resistente a vancomicina con genotipo vanB en el Hospital Clínico Regional de Concepción / Isolation of vancomycin resistant enterococcus faecium with genotype vanB at the Hospital Clínico Regional de Concepción

La resistencia bacteriana a los agentes antimicrobianos ha aumentado durante las últimas décadas. De particular importancia es la descripción de aislamientos de Enterococcus resistente a vancomicina (EVR), de reciente y progresiva descripción en nuestro país. Comunicamos el aislamiento de dos cepas de E. faecium resistentes a vancomicina de pacientes colonizados por este microorganismo en el Hospital Clínico Regional de Concepción. El estudio feno y genotípico fue positivo para vanB, además ambos aislamientos presentaron similitud genética en un estudio de tipificación molecular por rep-PCR. Interesantemente el aislamiento de estas cepas precedió al aislamiento de EVR según el protocolo ministerial. Esta diferencia puede explicarse por los factores de riesgo que presentaron los pacientes estudiados