[Colistin in the post-antibiotic era]. / Colistín en la era post-antibiótica.

One of the most important features of the post-antibiotic era in the late 20th century is the resurgence of colistin for the treatment of extensively drug resistant gram-negative bacteria (XDR). Colistin is a narrow spectrum anti-biotic, active against microorganisms with clinical significance such as Acinetobacter baumannii, Pseudomonas aeruginosa and Klebsiella pneumoniae. Nowadays its toxicity is lower, partly explained by better pharmaceuticals and management of the critically ill patients. However, there has been much confusion regarding the dosage of the drug, its name and labeling, therefore, experts have recommended using a common language about this polymyxin. The lack of PK/PD studies for colistin is perhaps the main weakness of this area of knowledge, even though the before mentioned approach has contributed with new ways to manage and calculate the dose of this antimicrobial. Indeed, the efficiency of colistin in association with a second agent in reducing mortality has not been demonstrated.

Colistín en la era post-antibiótica / Colistin in the post-antibiotic era

One of the most important features of the post-antibiotic era in the late 20th century is the resurgence of colistin for the treatment of extensively drug resistant gram-negative bacteria (XDR). Colistin is a narrow spectrum anti-biotic, active against microorganisms with clinical significance such as Acinetobacter baumannii, Pseudomonas aeruginosa and Klebsiella pneumoniae. Nowadays its toxicity is lower, partly explained by better pharmaceuticals and management of the critically ill patients. However, there has been much confusion regarding the dosage of the drug, its name and labeling, therefore, experts have recommended using a common language about this polymyxin. The lack of PK/PD studies for colistin is perhaps the main weakness of this area of knowledge, even though the before mentioned approach has contributed with new ways to manage and calculate the dose of this antimicrobial. Indeed, the efficiency of colistin in association with a second agent in reducing mortality has not been demonstrated.

El resurgimiento de colistín para el tratamiento de bacilos gramnegativos extensamente resistentes a antimicrobianos a fines del siglo pasado es una de las características más importantes de la era post-antimicrobiana. Su espectro es reducido y cubre microorganismos con importancia clínica como Acinetobacter baumannii, Pseudomonas aeruginosa y Klebsiella pneumoniae. En contraste a lo que se vio en el pasado, la toxicidad descrita en la actualidad es menor, en parte explicado por las mejores preparaciones farmacéuticas y la optimización del manejo del paciente crítico. Mucha confusión se ha generado respecto a la dosificación del fármaco, debido a la distinta denominación, etiquetado y sugerencias de los laboratorios, a pesar de que el compuesto es el mismo. Por lo anterior, el llamado de los expertos es a utilizar un lenguaje común para referirnos a esta polimixina. Los estudios modernos de PK/PD han contribuido con nuevas formas de administrar y calcular las dosis de este antimicrobiano; no obstante, falta mucho por desarrollar en esta área que se posiciona como su gran debilidad. A pesar que la terapia combinada se sustenta sobre una base teórica lógica, no se ha demostrado que la asociación de colistín con un segundo agente logre disminuir la mortalidad.

[Isolation of Staphylococcus aureus hetero-resistant to vancomycin (hVISA) in the Regional Hospital of Concepción, Chile]. / Aislamiento de Staphylococcus aureus hetero-resistente a vancomicina en Hospital Clínico Regional de Concepción, Chile.

Methicillin-resistant Staphylococcus aureus (MRSA) is widely distributed in hospital environments, causing serious infections, mainly the bloodstream, surgical site infection and pneumonia. Vancomycin (VAN) is the antibiotic of choice for treating severe MRSA infections; however, nowadays worldwide resistant strains (VRSA), with intermediate susceptibility (VISA) and decreased susceptibility or hetero-resistance to VAN (hVISA) have been reported, related to treatment failure and increased mortality. This report describes the first confirmed isolation of MRSA with hVISA phenotype in a public hospital in Chile.

[Antimicrobial susceptibility in Chile 2012]. / Susceptibilidad antimicrobiana en Chile 2012.

Bacteria antimicrobial resistance is an uncontrolled public health problem that progressively increases its magnitude and complexity. The Grupo Colaborativo de Resistencia, formed by a join of experts that represent 39 Chilean health institutions has been concerned with bacteria antimicrobial susceptibility in our country since 2008. In this document we present in vitro bacterial susceptibility accumulated during year 2012 belonging to 28 national health institutions that represent about 36% of hospital discharges in Chile. We consider of major importance to report periodically bacteria susceptibility so to keep the medical community updated to achieve target the empirical antimicrobial therapies and the control measures and prevention of the dissemination of multiresistant strains.

Susceptibilidad antimicrobiana en Chile 2012 / Antimicrobial susceptibility in Chile 2012

Bacteria antimicrobial resistance is an uncontrolled public health problem that progressively increases its magnitude and complexity. The Grupo Colaborativo de Resistencia, formed by a join of experts that represent 39 Chilean health institutions has been concerned with bacteria antimicrobial susceptibility in our country since 2008. In this document we present in vitro bacterial susceptibility accumulated during year 2012 belonging to 28 national health institutions that represent about 36% of hospital discharges in Chile. We consider of major importance to report periodically bacteria susceptibility so to keep the medical community updated to achieve target the empirical antimicrobial therapies and the control measures and prevention of the dissemination of multiresistant strains.

La resistencia bacteriana es un problema de salud pública que lejos de estar controlado, aumenta en cantidad y complejidad. El Grupo Colaborativo de Resistencia, es un conjunto de profesionales que representan a 39 establecimientos de salud del país y que se ha ocupado desde 2008 de recolectar información sobre la susceptibilidad antimicrobiana de bacterias en Chile. En este documento se presenta la susceptibilidad in vitro acumulada del año 2012, de 28 establecimientos de salud del país que representan, al menos, 36% de los egresos hospitalarios de Chile. Consideramos de la mayor relevancia reportar periódicamente la susceptibilidad bacteriana de modo de mantener a la comunidad médica actualizada para orientar las terapias empíricas y las medidas de control y prevención de la diseminación de cepas multi-resistentes.

Antibacterial activity of the Antarctic bacterium Janthinobacterium sp: SMN 33. 6 against multi-resistant Gram-negative bacteria

Background The increment of resistant strains to commonly used antibiotics in clinical practices places in evidence the urgent need to search for new compounds with antibacterial activity. The adaptations that Antarctic microorganisms have developed, due to the extreme environment that they inhabit, promote them as a potential new source of active compounds for the control of microorganisms causing infections associated with health care. The aim of this study was to evaluate the antibacterial activity of an ethanol extract of the Antarctic bacterium Janthinobacterium sp., strain SMN 33.6, against nosocomial multi-resistant Gram-negative bacteria. Results Inhibitory activity against human Gram-negative bacterial pathogens, with concentrations that varied between 0.5 and 16 µg ml- 1, was demonstrated. Conclusions The ethanolic extract of Janthinobacterium sp. SMN 33.6 possesses antibacterial activity against a chromosomal AmpC beta-lactamase-producing strain of Serratia marcescens, an extended-spectrum beta-lactamase-producing Escherichia coli and also against carbapenemase-producing strains of Acinetobacter baumannii and Pseudomonas aeruginosa. This becomes a potential and interesting biotechnological tool for the control of bacteria with multi-resistance to commonly used antibiotics.

[Main virulence factors of Listeria monocytogenes and its regulation]. / Principales factores de virulencia de Listeria monocytogenesy su regulación.

Listeria monocytogenesis a facultative intracellular pathogen, ubiquitous and aetiological agent of listeriosis. The main way of acquisition is the consumption of contaminated food and can cause serious medical conditions such as septicemia, meningitis and gastroenteritis, especially in children, immunocompromised individuals and seniors and abortions in pregnant women. An increase in cases of listeriosis worldwide has been reported and it is estimated that its prevalence in developed countries is in the range of 2 to 15 cases per one million population. This microorganism is characterized for the transition from the environment into the eukaryotic cell. Several virulence factors have been involved in the intracellular cycle that are regulated, primarily, by the PrfA protein, which in turn is regulated by different mechanisms operating at the transcriptional, translational and post-translational levels. Additionally, other regulatory mechanisms have been described as sigma factor, system VirR/S and antisense RNA, but PrfA is the most important control mechanism and is required for the expression of essential virulence factors for the intracellular cycle.

Principales factores de virulencia de Listeria monocytogenesy su regulación / Main virulence factors of Listeria monocytogenesand its regulation

Listeria monocytogenesis a facultative intracellular pathogen, ubiquitous and aetiological agent of listeriosis. The main way of acquisition is the consumption of contaminated food and can cause serious medical conditions such as septicemia, meningitis and gastroenteritis, especially in children, immunocompromised individuals and seniors and abortions in pregnant women. An increase in cases of listeriosis worldwide has been reported and it is estimated that its prevalence in developed countries is in the range of 2 to 15 cases per one million population. This microorganism is characterized for the transition from the environment into the eukaryotic cell. Several virulence factors have been involved in the intracellular cycle that are regulated, pimarilly, by the PrfA protein, which in turn is regulated by different mechanisms operating at the transcriptional, translational and post-translational levels. Additionally, other regulatory mechanisms have been described as sigma factor, system VirR/S and antisense RNA, but PrfA is the most important control mechanism and is required for the expression of essential virulence factors for the intracellular cycle.

Listeria monocytogeneses un patógeno intracelular facultativo, ubicuo y agente etiológico de listeriosis. La principal vía de adquisición es el consumo de alimentos contaminados, pudiendo ocasionar cuadros clínicos muy graves como septicemia, meningitis y gastroenteritis, especialmente en niños, individuos inmunocomprometidos y de la tercera edad, y aborto en mujeres embarazadas. Se ha informado un aumento en los casos de listeriosis a escala mundial y se estima que su frecuencia en los países desarrollados está en un rango de 2 a 15 casos por millón de habitantes. Este microorganismo se caracteriza por realizar una transición desde el medio ambiente hacia la célula eucariota. Para este proceso se han descrito varios factores de virulencia, los cuales están involucrados en el ciclo intracelular y están regulados, principalmente, por la proteína PrfA, la cual a su vez está regulada por diferentes mecanismos que actúan a nivel transcripcional, traduccional y post-traduccional. Además, se han descrito otros mecanismos regulatorios como: factor Sigma, sistema VirR/S y ARN sin sentido. No obstante, PrfA es el mecanismo de control más importante y el cual es requerido para la expresión de los factores de virulencia esenciales para el ciclo intracelular.

[The pneumococcal connection]. / La conexión neumocóccica.

The resistance of gram-negative bacilli is one of the most important areas in modern medicine, however it hasn't been highlighted the role of the third generation cephalosporins and in particularly ceftriaxone in the selection of gram-negative bacilli resistant to these agents. Paradoxically, ceftriaxone, like the rest of the molecules of this generation, whose initial indication were gram- negative infections began to be used as an agent of choice in pneumococcal infections. The broad spectrum activity of this molecule with its favorable pharmacokinetic properties replaces other agents by this antibiotic in the treatment of a wide range of community acquired infections. However, it wasn't considered the action of this cephalosporin on the microbiome, particularly the intestinal flora, which allowed the selection of enterobacteria that by genetic events, especially parental ß-lactamases mutations (TEM-1, TEM-2, SHV-1), developed resistance to third-generation cephalosporins. The decreased susceptibility to penicillin in Streptococcus pneumoniae isolates that stimulated the growing use of ceftriaxone, was one of the main drivers for the development of resistance to third-generation cephalosporins in gram-negative bacilli.

Spreading of AbaR-type genomic islands in multidrug resistance Acinetobacter baumannii strains belonging to different clonal complexes.

In order to determine the occurrence of AbaR-type genomic island in multidrug resistant Acinetobacter baumannii (MDRAb) strains circulating in Argentina, Uruguay, and Chile, we studied 51 MDRAb isolates recovered from several hospitals over 30 years. AbaR-type genomic resistance islands were found in 36 MDRAb isolates since 1986 till now. MLST technique allowed us to identify the presence of four different Clonal Complexes (109, 104, 119, 113) among the positive AbaR-type island positive strains. This is the first description of AbaR-type islands in the CC104 and CC113 that are the most widespread Clonal Complexes in Argentina. In addition, PCR mapping exposed different arrays to those previously described, evidencing the plasticity of this island. Our results evidence a widespread distribution of the AbaR-type genomic islands along the time in the MDRAb population, including the epidemic global clone 1 (GC1) as well as different clonal complexes to those already described in the literature.

Actividad de cobre sobre bacilos gramnegativos multi-resistentes aislados en hospitales chilenos / Copper activity against multiresistant Gram negative bacilli isolated from Chilean hospitals

Introduction: Multiresistant nosocomial pathogens, especially Gram-negative bacilli (GNB), are a serious problem for public health systems worldwide. Due to their antimicrobial properties, copper alloys have been suggested as an alternative for the control of bacterial burden in surfaces in hospital environment. However, antibiotic multiresistance and copper resistance could be associated in GNB, and there is evidence that both kind of resistance genes (antibiotic and copper) can be located on the same genetic structures. For this reason antibiotic-multiresistant strains could survive in the presence of copper, selecting for bacterial phenotypes resistant to both antibacterial agents. Aim: To evaluate antibacterial activity of copper against nosocomial extended-spectrum β-lactamases (ESBL) (+) and ESBL (-) GNB, and carbapenems resistant or susceptible strains. Material and Method: This study included 390 strains of GNB isolated from Chilean hospitals: Acinetobacter baumannii and Pseudomonas aeruginosa resistant (CAR R) and susceptible (CAR S) to carbapenem antibiotics, and Klebsiella pneumoniae and Escherichia coli producers and non-producers of ESBL. Susceptibility levels to cupric sulphate were determined by agar dilution method and statistical analysis were used to determine the significance of the differences in the copper tolerance levels between the strains groups. Results: Statistically superior copper tolerance levels were found in the CAR R and ESBL producing strains of A. baumannii and K. pneumoniae, in relation with the CAR S and ESBL not-producing strains. Conclusion: A relation between a diminished susceptibility to ionic copper and to recent generation antimicrobial agents was observed in K. pneumoniae y A. baumannii strains.

Introducción: Los patógenos intrahospitalarios multi-resistentes constituyen un grave problema mundial de salud pública, especialmente los bacilos gramnegativos (BGN). El uso de cobre como antimicrobiano de superficie en hospitales se postula como una alternativa para el control de microorganismos en estos ambientes. Sin embargo, la multi-resistencia a antimicrobianos en BGN hospitalarios puede asociarse con la tolerancia a cobre, ya que existe evidencia que genes que codifican tolerancia a este metal pueden encontrarse en elementos genéticos que confieren resistencia a antimicrobianos. Por esta razón, cepas multi-resistentes a antimicrobianos podrían sobrevivir en presencia de cobre, seleccionando bacterias resistentes a ambos agentes antibacterianos. Objetivo: Investigar la actividad de cobre sobre BGN hospitalarios productores y no productores de β-lactamasas de espectro extendido (BLEE), y resistentes o susceptibles a antimicrobianos carbapenémicos. Material y Métodos: Se estudió 390 cepas de BGN aisladas en hospitales chilenos: Acinetobacter baumannii y Pseudomonas aeruginosa resistentes (CAR R) y susceptibles (CAR S) a carbapenémicos y Klebsiella pneumoniae y Escherichia coli productoras y no productoras de BLEE. Se investigó los niveles de susceptibilidad a sulfato cúprico, mediante dilución seriada en agar y se evaluó la significancia estadística de la diferencia de estos niveles entre los distintos grupos de cepas. Resultados: Se encontraron niveles de tolerancia a cobre superiores en cepas de A. baumannii y K. pneumoniae, CAR R y productoras de BLEE respectivamente, con respecto a sus pares CAR S y no productoras de BLEE. Conclusión: Observamos una relación entre la disminución de la susceptibilidad a cobre iónico y a antimicrobianos de última generación en K. pneumoniae y A. baumannii.

OXA-type carbapenemases in Acinetobacter baumannii in South America.

Acinetobacter baumannii is an opportunistic pathogen that is frequently involved in outbreaks of infection, occurring mostly in intensive care units. The increasing incidence of carbapenem resistance in A. baumannii worldwide is a concern since it limits drastically the range of therapeutic alternatives. The most important mechanism of carbapenem resistance is the enzymatic hydrolysis mediated by carbapenemases. In A. baumannii these enzymes are usually OXA-type carbapenemases, and belong to class D according to the classification of Ambler. The OXA-type carbapenemases are divided into five subgroups, four of which correspond to acquired carbapenemases, which accounts for the distribution of genes blaOXA in different geographic areas. In this work we review the different types of OXA-type carbapenemases present in A. baumannii, emphasizing the current situation in South America with special mention to the findings in Chile.

[Copper activity against multiresistant Gram negative bacilli isolated from Chilean hospitals]. / Actividad de cobre sobre bacilos gramnegativos multi-resistentes aislados en hospitales chilenos.

INTRODUCTION: Multiresistant nosocomial pathogens, especially Gram-negative bacilli (GNB), are a serious problem for public health systems worldwide. Due to their antimicrobial properties, copper alloys have been suggested as an alternative for the control of bacterial burden in surfaces in hospital environment. However, antibiotic multiresistance and copper resistance could be associated in GNB, and there is evidence that both kind of resistance genes (antibiotic and copper) can be located on the same genetic structures. For this reason antibiotic-multiresistant strains could survive in the presence of copper, selecting for bacterial phenotypes resistant to both antibacterial agents. AIM: To evaluate antibacterial activity of copper against nosocomial extended-spectrum ß-lactamases (ESBL) (+) and ESBL (-) GNB, and carbapenems resistant or susceptible strains. MATERIAL AND METHOD: This study included 390 strains of GNB isolated from Chilean hospitals: Acinetobacter baumannii and Pseudomonas aeruginosa resistant (CAR R) and susceptible (CAR S) to carbapenem antibiotics, and Klebsiella pneumoniae and Escherichia coli producers and non-producers of ESBL. Susceptibility levels to cupric sulphate were determined by agar dilution method and statistical analysis were used to determine the significance of the differences in the copper tolerance levels between the strains groups. RESULTS: Statistically superior copper tolerance levels were found in the CAR R and ESBL producing strains of A. baumannii and K. pneumoniae, in relation with the CAR S and ESBL not-producing strains. CONCLUSION: A relation between a diminished susceptibility to ionic copper and to recent generation antimicrobial agents was observed in K. pneumoniae y A. baumannii strains.

Characterization of Vibrio parahaemolyticus strains isolated in Chile in 2005 and in 2007.

INTRODUCTION: Vibrio (V.) parahaemolyticus has endemically established in Chilean sea shores, causing outbreaks every year, with an important number of cases. In order to know the genetic relationship, genotype dominance and antibiotic resistance of isolates obtained from two outbreaks, this study characterized 110 strains isolated from environmental and clinical samples in years 2005 and 2007 in Chile. METHODOLOGY: Genotyping was performed by determination of PFGE profiles, and pandemic group and integrons were screened by PCR. Antimicrobial susceptibility was studied by the disk diffusion method. RESULTS: High antibiotic susceptibility frequency was found, mainly among 2007 isolates, except to ampicillin, cephalothin, cefoxitin, cefpodoxime, amikacin, streptomycin and kanamycin. Strains belonging to the pandemic group in clinical isolates account for 88% in 2005, decreasing to 66% in 2007 and among environmental isolates were detected in 20% of the strains from 2005, rising to 36% in 2007. In 2005, nine different PFGE profiles were identified, with 78% of the strains corresponding to a single clone. In 2007, sixteen different PFGE profiles were detected, with 61% of the strains included into a sole clone. The same clone was prevalent in both years. None of class 1, 2, 3 and SXT integrases genes was detected; however, the superintegron integrase gene (intIA) was present in almost all strains. CONCLUSIONS: These results suggest the persistence and dominance of a unique PFGE clone of V. parahaemolyticus during 2005 and 2007, and the absence of genetic elements that capture antibiotic resistance genes described in other species of Vibrio.

[Multi-drug efflux pumps and antibiotic resistance in Acinetobacter baumannii]. / Bombas de expulsión multidrogas en Acinetobacter baumannii y resistencia a antimicrobianos.

Bacterial multi-drugs systems contribute to the development of multi-resistance patterns of Acinetobacter baumannii, a nosocomial pathogen of increasing importance due to its emerging resistance to carbapenems. The multi-resistance phenomena is generated by a combination of mechanisms, one of which the efflux pump system. Many of these multiresistant isolates of A. baumannii harbor genes for the AdeABC multi-drug efflux system, related with resistance to various groups of antibacterial agents, including tygecicline and meropenem. Inhibition of these systems would allow to increase the efficacy of this antimicrobial. This review focuses on the multi-drug efflux pump system of A. baumannii with special emphasis in the AdeABC system.

Extended-spectrum beta-lactamases belonging to CTX-M group produced by Escherichia coli strains isolated from companion animals treated with enrofloxacin.

We studied the antibiotic resistance among Escherichia coli isolates obtained from fecal samples of dogs and cats treated and untreated with enrofloxacin in veterinary clinics. Resistant patterns of 70 strains and the presence of extended-spectrum beta-lactamase (ESBL) were studied. The genes encoding the following families of beta-lactamases: CTX-M, GES, PER, TEM and SHV, were investigated by PCR-RFLP and sequencing. The strains isolated from enrofloxacin-treated animals were multi-drug-resistant exhibiting resistant patterns including fluorquinolones, beta-lactams, aminoglycosides, tetracycline and phenicols. On the contrary, the strains obtained from the untreated group of animals exhibited narrower antibiotic resistant profiles. The synthesis of ESBL was detected in 14 strains (20%) isolated from treated animals. The ESBL encoded by genes bla CTX-M-1, bla CTX-M-9 group and bla PER-2 were detected by PCR. We believe that this is the first report on the presence of ESBL in E. coli strains isolated from small animals in Chile, and the first report of beta-lactamase belonging to the CTX-M-9 group (CTX-M-14). The presence of these genes in bacteria isolated from pets is an important fact that constitutes a public health concern.

[Molecular identification of aminoglycoside-modifying enzymes among strains of Enterococcus spp. isolated in hospitals of the VIII Region of Chile]. / Identificación molecular de enzimas modificantes de aminoglucósidos en cepas de Enterococcus spp. aisladas en hospitales de la Octava Región de Chile.

BACKGROUND: Infectious diseases produced by Enterococcus spp, must be treated with a synergistic combination between a penicillin and an aminoglycoside. High level resistance to aminoglycosides is a serious therapeutic problem, since it predicts the loss of synergistic activity of this antimicrobial combination. AIM: To investigate the presence of genes encoding aminoglycoside-modifying enzymes (AMEs) among strains of Enterococcus spp with high level of resistance to aminoglycosides. MATERIAL AND METHODS: The genes encoding some of the AMEs were investigated among 305 aminoglycoside-resistant strains of Enterococcus spp isolated in hospitals of the VIII region of Chile, by dot blot hybridization and Polymerase Chain Reaction (PCS). RESULTS: High level resistance to some aminoglycosides was observed in 104 strains (34.1 %) and 93 of these harbored at least one of the genes encoding the investigated AMEs. Three genes were detected: aac(6)Ie-aph(2")Ia (14.8%) encoding for the enzyme AAC(6)Ie-APH(2")Ia (resistance to all aminoglycosides, except streptomycin); aph(3)IIIa (26%), and ant(6)la (28.5%) encoding for the phosphorylating enzymes APH(3)Ilia (resistance to kanamycin, amikacin and neomycin), and ANT(6)-la (resistance only to streptomycin), respectively. None of the strains harbored the gene ant (4) which encode for the enzyme ANT (4). CONCLUSION: The low frequency of strains harbouring the bifunctional enzyme (<15%), conferring an extended resistance profile to aminoglycosides, allows us to propose the empirical use of aminoglycoside-aminocyclitols, associated to a penicillin, in the treatment of serious infections produced by species of enterococci.