Post-antibiotic era in hemodialysis? Two case reports of simultaneous colonization and bacteremia by multidrug-resistant bacteria / Era pós-antibiótica em hemodiálise? Relato de dois casos de colonização simultânea e bacteremia por bactérias multirresistentes

ABSTRACT The emergence of resistance mechanisms not only limits the therapeutic options for common bacterial infections but also worsens the prognosis in patients who have conditions that increase the risk of bacterial infections. Thus, the effectiveness of important medical advances that seek to improve the quality of life of patients with chronic diseases is threatened. We report the simultaneous colonization and bacteremia by multidrug-resistant bacteria in two hemodialysis patients. The first patient was colonized by carbapenem- and colistin-resistant Klebsiella pneumoniae, carbapenem-resistant Pseudomonas aeruginosa, and methicillin-resistant Staphylococcus aureus (MRSA). The patient had a bacteremia by MRSA, and molecular typing methods confirmed the colonizing isolate was the same strain that caused infection. The second case is of a patient colonized by extended-spectrum beta-lactamases (ESBL)-producing Escherichia coli and carbapenem-resistant Pseudomonas aeruginosa. During the follow-up period, the patient presented three episodes of bacteremia, one of these caused by ESBL-producing E. coli. Molecular methods confirmed colonization by the same clone of ESBL-producing E. coli at two time points, but with a different genetic pattern to the strain isolated from the blood culture. Colonization by multidrug-resistant bacteria allows not only the spread of these microorganisms, but also increases the subsequent risk of infections with limited treatments options. In addition to infection control measures, it is important to establish policies for the prudent use of antibiotics in dialysis units.

RESUMO O surgimento de mecanismos de resistência não apenas limita as opções terapêuticas para infecções bacterianas comuns, mas também piora o prognóstico em indivíduos com condições que aumentam o risco de infecções bacterianas. Assim, a eficácia de importantes avanços médicos que buscam melhorar a qualidade de vida de pacientes com doenças crônicas está ameaçada. Relatamos a colonização e bacteremia simultâneas por bactérias multirresistentes em dois pacientes em hemodiálise. O primeiro paciente foi colonizado por Klebsiella pneumoniae resistente a carbapenem e colistina, Pseudomonas aeruginosa resistente a carbapenem e Staphylococcus aureus resistente a meticilina (MRSA). O paciente apresentou bacteremia por MRSA, e os métodos de tipagem molecular confirmaram que o isolado colonizador era a mesma cepa que estava causando infecção. O segundo caso é de um paciente colonizado por Escherichia coli produtora de beta-lactamases de espectro estendido (ESBL) e Pseudomonas aeruginosa resistente ao carbapenem. Durante o período de seguimento, o paciente apresentou três episódios de bacteremia, um deles causado por E. coli produtora de ESBL. Os métodos moleculares confirmaram a colonização pelo mesmo clone de E. coli produtora de ESBL em dois momentos, mas com um padrão genético diferente da cepa isolada da hemocultura. A colonização por bactérias multirresistentes aumenta o potencial não apenas da disseminação desses microrganismos, mas também do risco subsequente de infecções com opções limitadas de tratamentos. Além das medidas de controle de infecção, é importante estabelecer políticas para o uso prudente de antibióticos nas unidades de diálise.

Guía de Práctica Clínica para el Diagnóstico y Manejo de las Infecciones de Piel y Tejidos Blandos en Colombia / Clinical Practice Guidelines for the Diagnosis and Management of Skin and Soft Tissue Infections in Colombia

Las infecciones de piel y tejidos blandos (IPTB) representan la tercera causa de consulta por enfermedad infecciosas a los servicios médicos, después de las infecciones respiratorias y urinarias. Se presenta una guía de práctica clínica (GPC) con 38 recomendaciones basadas en la evidencia, graduadas bajo el sistema SIGN, para el diagnóstico y tratamiento de pacientes adultos con IPTB en el contexto colombiano, posterior a un proceso de adaptación de GPC publicadas y la búsqueda sistemática y síntesis de literatura para la actualización de la evidencia científica. Además, se realizó un consenso de expertos para la evaluación de las potenciales barreras para la implementación de las recomendaciones y la evaluación del grado de recomendación en el contexto local.

Skin and soft tissue infections (SSTI) represent the third leading cause of infectious disease consultation for medical services after respiratory and urinary tract infections. This document generates a clinical practice guideline with 38 recommendations based on evidence, graduated under the SIGN system for the diagnosis and treatment for SSTI infections in adult patients in Colombia, following a process of adaptation of guidelines published, and the systematic search and synthesis of literature for the updating of scientific evidence. In addition, a consensus of experts was made for the evaluation of the potential barriers for the implementation of the recommendations and the evaluation of the degree of recommendation in the local context.

High frequency of methicillin-susceptible and methicillin-resistant Staphylococcus aureus in children under 1 year old with skin and soft tissue infections / Alta frequência de S. aureus (MSSA-MRSA) em crianças com menos de um ano deidade com infecções de pele e do tecido mole

Abstract Objective: Staphylococcus aureus is responsible for a large number of infections in pediatric population; however, information about the behavior of such infections in this population is limited. The aim of the study was to describe the clinical, epidemiological, and molecular characteristics of infections caused by methicillin-susceptible and resistant S. aureus (MSSA-MRSA) in a pediatric population. Method: A cross-sectional descriptive study in patients from birth to 14 years of age from three high-complexity institutions was conducted (2008-2010). All patients infected with methicillin-resistant S. aureus and a representative sample of patients infected with methicillin-susceptible S. aureus were included. Clinical and epidemiological information was obtained from medical records and molecular characterization included spa typing, pulsed-field gel electrophoresis (PFGE), and multilocus sequence typing (MLST). In addition, staphylococcal cassette chromosome mec (SCCmec) and virulence factor genes were detected. Results: A total of 182 patients, 65 with methicillin-susceptible S. aureus infections and 117 with methicillin-resistant S. aureus infections, were included in the study; 41.4% of the patients being under 1 year. The most frequent infections were of the skin and soft tissues. Backgrounds such as having stayed in day care centers and previous use of antibiotics were more common in patients with methicillin-resistant S. aureus infections (p ≤ 0.05). Sixteen clonal complexes were identified and methicillin-susceptible S. aureus strains were more diverse. The most common cassette was staphylococcal cassette chromosomemec IVc (70.8%), which was linked to Panton-Valentine leukocidin (pvl). Conclusions: In contrast with other locations, a prevalence of infections in children under 1 year of age in the city could be observed; this emphasizes the importance of epidemiological knowledge at the local level.

Resumo Objetivo: O Staphylococcus aureus é responsável por um grande número de infecções na população pediátrica; contudo, as informações sobre o comportamento dessas infecções nessa população são limitadas. O objetivo do estudo foi descrever as características clínicas, epidemiológicas e moleculares de infecções causadas por Staphylococcus aureus suscetíveis e resistentes à meticilina (MSSA-MSRA) em uma população pediátrica. Método: Um estudo transversal descritivo foi realizado em pacientes entre 0 e 14 anos de idade de três instituições de alta complexidade (2008-2010). Todos os pacientes infectados com S. aureus resistentes à meticilina e uma amostra representativa de pacientes infectados com S. aureus suscetíveis à meticilina foram incluídos. As informações clínicas e epidemiológicas foram obtidas de prontuários médicos, e a caracterização molecular incluiu tipagem spa, Eletroforese em Gel de Campo Pulsado (PFGE) e Tipagem de sequências multilocus (MLST). Além disso, o Cassete Cromossômico Estafilocócico mec (SCCmec) e genes de fatores de virulência foram detectados. Resultados: 182 pacientes, 65 com infecções por S. aureus suscetíveis à meticilina e 117 com infecções por S. aureus resistentes à meticilina, foram incluídos no estudo; 41,4% dos pacientes com menos de um ano de idade. As infecções mais frequentes foram da pele e dos tecidos moles. Os históricos como internações em centros de atendimento e o uso prévio de antibióticos foram mais comuns em pacientes com infecções por S. aureus resistentes à meticilina (p ≤ 0,05). Dezesseis complexos clonais foram identificados, e as cepas de S. aureus suscetíveis à meticilina foram mais diversificadas. O cassete mais comum foi o Cassete Cromossômico Estafilocócicomec IVc (70,8%), relacionado à leucocidina de panton-valentine (pvl). Conclusões: Em comparação a outros locais, observamos uma prevalência de infecções em crianças com menos de um ano de idade na cidade; o que enfatiza a importância de conhecer a epidemiologia em nível local.

Caracterización molecular de un brote de Klebsiella pneumoniae resistente a carbapenémicos en un hospital de alto nivel de complejidad de Medellín, Colombia / Molecular characterization of an outbreak of carbapenem-resistant Klebsiella pneumoniae in a tertiary care hospital in Medellín, Colombia

Introducción. La resistencia a los carbapenémicos constituye una seria amenaza para la salud pública a nivel mundial, ya que estos antibióticos son una de las últimas opciones terapéuticas contra las bacterias multirresistentes. La caracterización molecular de los brotes causados por bacterias resistentes aporta información relevante para el diseño de estrategias de control de infecciones. Objetivo. Describir las características moleculares de un brote de Klebsiella pneumoniae resistente a carbapenémicos ocurrido en un hospital de alto nivel de complejidad de Medellín entre 2010 y 2011. Materiales y métodos. A partir de una colección de cepas del brote ocurrido en la institución hospitalaria, se recuperaron 84 aislamientos de 32 pacientes infectados y 52 colonizados. La identificación y la sensibilidad de los aislamientos se establecieron mediante el sistema Vitek2 ® . La detección de carbapenemasas se hizo mediante el test de Hodge modificado y usando la reacción en cadena de la polimerasa. La relación genética entre los aislamientos se evaluó mediante electroforesis en gel de campo pulsado y tipificación de secuencias de locus múltiple. Resultados. Todos los aislamientos analizados fueron multirresistentes; el análisis molecular reveló que todos eran portadores del gen bla KPC-3 . El análisis genético mostró que los aislamientos de pacientes infectados y colonizados (58/64 aislamientos) estaban estrechamente relacionados (>80 %) y pertenecían al linaje ST258. Conclusión. Mediante el empleo de técnicas de tipificación molecular fue posible confirmar un brote ocasionado por K. pneumoniae ST258 portador del bla KPC-3 con un perfil de multirresistencia, el cual había sido asociado a uno anterior ocurrido en otro hospital de Medellín. El ST258 es un clon de alto riesgo presente a nivel mundial, lo que debe alertar sobre la posible diseminación de resistencia en el país. El empleo de herramientas moleculares en la vigilancia epidemiológica, es útil para evaluar la diseminación de microorganismos de interés en salud pública.

Introduction: Resistance to carbapenems is considered to represent a serious threat to public health at the global level, since these antibiotics are one of the last therapeutic options for the treatment of multidrug-resistant bacteria. Molecular characterization of outbreaks due to resistant bacteria provides information that can be used in the design of infection control strategies. Objective: To describe the molecular characteristics of an outbreak of carbapenem-resistant Klebsiella pneumoniae that occurred in a tertiary care hospital in Medellín in 2010-2011. Materials and methods: Eighty-four isolates were obtained from a collection of strains associated with the hospital outbreak, of which 32 were from patients infected at that time and 52 were carriers. Identification and susceptibility of the isolates was performed using Vitek2 ® . Carbapenemases were detected using a modified Hodge test and polymerase chain reaction. Genetic relationships between the isolates were evaluated using pulsed field gel electrophoresis and multiple locus sequence typing. Results: All the isolates analyzed were multidrug resistant; molecular analysis revealed that all harbored bla KPC-3 . The genetic analysis showed that 58/64 of the isolates from both infected and colonized patients were closely related (Dice similarity index >80%) and belonged to the ST258 lineage. Conclusion: Using molecular typing techniques it was possible to confirm the occurrence of an outbreak caused by K. pneumoniae ST258, a carrier of bla KPC-3 with a multidrug-resistant profile which had been associated with a previous outbreak in another hospital in the city of Medellín. ST258 is a high risk clone at the global level, demonstrating the potential for dissemination of resistance in this country. Implementation of molecular tools in support of epidemiological surveillance is useful for evaluating the spread of microorganisms of public health significance.

Acinetobacter baumannii resistente a carbapenémicos causante de osteomielitis e infecciones de la piel y los tejidos blandos en hospitales de Medellín, Colombia / Carbapenem-resistant Acinetobacter baumannii causing osteomyelitis and infections of skin and soft tissues in hospitals of Medellín, Colombia

Introducción. Acinetobacter baumannii es una bacteria oportunista que infecta a pacientes gravemente enfermos, principalmente con neumonía asociada al uso del respirador y bacteriemia. La aparición de resistencia a los carbapenémicos limita las opciones terapéuticas para el manejo de las infecciones ocasionadas por esta bacteria. Objetivo. Describir las características clínicas y moleculares de las infecciones ocasionadas por A. baumannii resistente a carbapenémicos en hospitales de Medellín. Materiales y métodos. Durante dos años se llevó a cabo un estudio descriptivo de corte transversal en cinco hospitales de Medellín. La información clínica provenía de las historias clínicas. La presencia de carbapenemasas se evaluó mediante el test tridimensional y la técnica de reacción en cadena de la polimerasa. La tipificación molecular se hizo con electroforesis en gel de campo pulsado y tipificación de secuencias de múltiples locus. Resultados. Se incluyeron 32 pacientes, 13 de los cuales presentaban infecciones de la piel y los tejidos blandos (n=7, 21,9 %), y osteomielitis (n=6, 18,7 %). Los porcentajes de resistencia fueron superiores a 80 % para todos los antibióticos evaluados, excepto para la colistina y la tigecilina. Las carbapenemasas OXA-23 y OXA-51, así como la secuencia de inserción IS Aba1 , se detectaron en todos los aislamientos. La electroforesis en gel de campo pulsado reveló una gran diversidad genética en los aislamientos, y la tipificación de secuencias de múltiples locus evidenció la circulación de los clones ST229 y ST758 en la ciudad. Conclusión. Contrario a lo reportado previamente, los resultados del estudio revelaron que la osteomielitis y las infecciones de la piel y los tejidos blandos eran los principales cuadros clínicos causados por A. baumannii resistente a carbapenémicos en instituciones de Medellín, y resaltan su importancia como agente etiológico de este tipo de infecciones.

Introduction: Acinetobacter baumannii is an opportunistic bacterium which infects seriously ill patients, particularly those with ventilator-associated pneumonia and bacteremia. The emergence of resistance to carbapenem limits the options for the treatment of infections caused by this bacterium. Objective: To describe the clinical and molecular characteristics of infections caused by carbapenem-resistant A. baumannii in Medellín hospitals. Materials and methods: A cross-sectional descriptive study was carried out in five Medellín hospitals over a 2-year period. Clinical information was obtained from medical histories of patients. The presence of carbapenemases was evaluated by three-dimensional test and PCR. Molecular typing was performed using PFGE and MLST. Results: The study included 32 patients, 13 of whom presented skin and soft tissue infections (n=7, 21.9%) or osteomyelitis (n=6, 18.7%). Resistance rates of the isolates exceeded 80% for all the antibiotics evaluated except colistin and tigecycline. Carbapenemases OXA-23 and OXA-51, as well as the insertion sequence IS Aba1 , were detected in all the isolates. PFGE revealed high genetic diversity in the isolates and MLST showed clones ST229 and ST758 are circulating in the city. Conclusion: In contrast to previous reports, the results of the present study showed osteomyelitis and infections of skin and soft tissues to be the main infections caused by carbapenem-resistant A. baumannii in Medellín hospitals and revealed its importance as an etiological agent for this type of infections.

Cambios a lo largo del tiempo en la distribución de los complejos de clones dominantes de Staphylococcus aureus resistente a la meticilina en Medellín, Colombia / Changes over time in the distribution of dominant clonal complexes of methicillin-resistant Staphylococcus aureus in Medellín, Colombia

Introducción. Parte del éxito de Staphylococcus aureus resistente a la meticilina (SARM) como patógeno se debe a la rápida diseminación de linajes pandémicos con perfiles variables de virulencia y sensibilidad antimicrobiana. En Colombia se han identificado clones asociados al hospital como el pediátrico (CC5-ST5-SCC mec IV), el brasilero (CC8-ST239-SCC mec III) y el chileno/cordobés (CC5-ST5-SCC mec I). Asimismo, se describió el USA300 (CC8-ST8-SCC mec IV), tradicionalmente asociado a la comunidad, causante de infecciones hospitalarias . Objetivo. Describir el comportamiento en el tiempo de los clones de SARM provenientes de un hospital universitario de Medellín en aislamientos recolectados con una década de diferencia. Materiales y métodos. Se analizaron 398 aislamientos de SARM, 67 recolectados en 1994 y 331 recolectados entre 2008 y 2010. La identificación y la sensibilidad a la meticilina se confirmaron mediante los genes nuc y mec A. La caracterización molecular incluyó la tipificación de spa , SCC mec , la electroforesis en gel de campo pulsado ( Pulsed Field Gel Electrophoresis, PFGE), y la tipificación por secuenciación de locus múltiples ( Multilocus Sequence Typing , MLST). Resultados. Al analizar los aislamientos de SARM de 1994 se encontró que pertenecían a un único linaje, el CC5-SCC mec IV, mientras que los aislamientos de 2008 a 2010 presentaron dos linajes dominantes: el CC8-SCC mec IVc, con cepas de los tipos spa t008 y t1610, estrechamente relacionadas con el clon USA 300, y el CC5-SCC mec I, con las de tipo spa t149, relacionadas con el clon chileno; no se detectaron cepas del linaje encontrado en 1994. Conclusiones. En este estudio se demuestra una dinámica en el tiempo de las cepas de S. aureus , y se señala la importancia de la vigilancia local y la difusión de los resultados, sobre todo en países como el nuestro, donde SARM es prevalente y la comprensión de su epidemiología es limitada.

Introduction: Part of the success of methicillin-resistant Staphylococcus aureus (MRSA) as a pathogen responds to the rapid spread of pandemic lineages with diverse virulence and antimicrobial susceptibility profiles. In Colombia, several healthcare-associated MRSA (HA-MRSA) clones have been found, including the pediatric clone (CC5-ST5-SCC mec IV), the Brazilian clone (CC8-ST239-SCC mec III), and the Chilean/Cordobés clone (CC5-ST5-SCC mec I). Moreover, the community-associated MRSA (CA-MRSA) clone USA300 has been reported as causing hospital-acquired infections. Objective: To describe the changes over time in the distribution of MRSA clones from a university hospital in Medellín collected at two time points a decade apart. Materials and methods: A total of 398 MRSA strains were analyzed. Of these, 67 strains were collected in 1994, while the remaining 331 strains were collected between 2008 and 2010. Species identification and methicillin resistance were confirmed by detection of nuc and mec A genes, respectively. Molecular characterization included spa typing, SCC mec typing, PFGE and MLST. Results: Analysis of the MRSA strains collected in 1994 revealed that they belonged to a single clone, the CC5-SCC mec IV, whereas among the isolates from 2008-2010, two dominant clones were identified: CC8-SCC mec IVc, which included spa types t008 and t1610 and is closely related to the USA 300 clone, and CC5-SCC mec I ( spa type t149), related to the Chilean clone. The ST5-SCC mec IV clone from 1994 was not detected. Conclusions: This study identifies temporal dynamics in MRSA clone diversity, and highlights the importance of local surveillance and dissemination of results, especially in countries like Colombia where MRSA is prevalent and knowledge regarding its epidemiology is still insufficient.

Characterisation of virulence genes in methicillin susceptible and resistant Staphylococcus aureus isolates from a paediatric population in a university hospital of Medellín, Colombia

Virulence and antibiotic resistance are significant determinants of the types of infections caused by Staphylococcus aureus and paediatric groups remain among the most commonly affected populations. The goal of this study was to characterise virulence genes of methicillin-susceptible S. aureus (MSSA) and methicillin-resistant S. aureus (MRSA) strains isolated from a paediatric population of a Colombian University Hospital during 2009. Sixty MSSA and MRSA isolates were obtained from paediatric patients between zero-14 years. We identified the genes encoding virulence factors, which included Panton-Valentine leucocidine (PVL), staphylococcal enterotoxins A-E, exfoliative toxins A and B and toxic shock syndrome toxin 1. Typing of the staphylococcal chromosome cassette mec (SCCmec) was performed in MRSA strains. The virulence genes were more diverse and frequent in MSSA than in MRSA isolates (83 percent vs. 73 percent). MRSA strains harboured SCCmec types IVc (60 percent), I (30 percent), IVa (7 percent) and V (3 percent). SCCmec type IVc isolates frequently carried the PVL encoding genes and harboured virulence determinants resembling susceptible strains while SCCmec type I isolates were often negative. PVL was not exclusive to skin and soft tissue infections. As previously suggested, these differences in the distribution of virulence factor genes may be due to the fitness cost associated with methicillin resistance.

Diversidad genética de Plasmodium falciparum y sus implicaciones en la epidemiología de la malaria / Genetic diversity of Plasmodium falciparum and its implications in the epidemiology of

La diversidad genética le confiere a Plasmodium falciparum la capacidad de evadir la respuestainmune del hospedero y producir variantes resistentes a medicamentos y a vacunas, aspectos que juegan un papel importante en el establecimiento de medidas de control contra la malaria. Diferentes autores han documentado la existencia de diversas cepas o clones de P. falciparum, cuya diversidad genética se ha confirmado a través de distintos ensayos de PCR (reacción en cadena de la polimerasa). Numerosas investigaciones realizadas en poblaciones con diferente grado de transmisión de malaria han mostrado la relación existente entre la estructura de la población de P. falciparum y la epidemiología de la enfermedad. En este artículo se describen las fases del ciclo de vida en las que los eventos de recombinación originan la diversidad genética de P. falciparum, se revisan los estudios realizados sobre este aspecto en regiones con diferentes grados de endemicidad, así como sobre sus implicaciones en la adquisición de inmunidad y en el desarrollo de medidas de control