Resistencia bacteriana a antibióticos en ambientes acuáticos: origen e implicaciones para la salud pública

El alarmante incremento de la resistencia bacteriana a los antibióticos a nivel global ha dilucidado otras fuentes diferentes al hospital y la comunidad, donde el agua ha cobrado gran importancia. El ambiente acuático constituye la fuente y el hábitat natural de un gran número de microorganismos, incluyendo bacterias resistentes a antibióticos; así mismo, se considera uno de los principales receptores de antimicrobianos, bacterias resistentes y genes de resistencia a antibióticos provenientes de las actividades humanas. La contaminación del agua con estos contaminantes emergentes tiene implicaciones serias para la salud humana, relacionadas con la diseminación de la resistencia bacteriana y la emergencia de nuevos mecanismos de resistencia. En esta revisión se brinda una descripción global del papel de los ambientes acuáticos en el problema de la resistencia bacteriana, las principales fuentes de contaminación, además del impacto para la salud pública. Ante este panorama, se establece la necesidad de abordar la problemática de la resistencia bacteriana desde la perspectiva de "una salud", donde a la vigilancia tradicional, enfocada a nivel humano y veterinario, se articule la vigilancia epidemiológica ambiental, principalmente basada en aguas residuales.

The alarming increase in bacterial resistance to antibiotics globally has diluted sources other than the hospital and community, where water has taken on great importance. The aquatic environment is the source and natural habitat of a large number of microorganisms, including antibiotic-resistant bacteria, as well as being considered one of the main receptors for antimicrobials, resistant bacteria and antibiotic resistance genes from human activities. Contamination of water with these emerging contaminants has serious implications for human health related to the spread of bacterial resistance and the emergence of new resistance mechanisms. This review provides a global description of the role of aquatic environments in the problem of bacterial resistance, the main sources of contamination, as well as the impact on Public Health. In this context, the need arises to address the problem of bacterial resistance from the perspective of "one health", where traditional surveillance, focused at the human and veterinary level, is articulated with environmental epidemiological surveillance, mainly in wastewater.

O incremento alarmante da resistência bacteriana aos antibióticos no nível global tem revelado outras fontes diferentes do hospital e da comunidade, em que a água tem ganho grande importância. O ambiente aquático constitui a fonte e o hábitat natural de um grande número de microrganismos, incluindo bactérias resistentes a antibióticos; é considerado, também, um dos principais receptores de antimicrobianos, bactérias resistentes e genes de resistência a antibióticos provindos das atividades humanas. A poluição da água com esses poluentes emergentes tem sérias implicações para a saúde humana, relacionadas com a disseminação da resistência bacteriana e a emergência de novos mecanismos de resistência. Nesta revisão oferece-se uma descrição global do papel dos ambientes aquáticos na situação problemática da resistência bacteriana, as principais fontes de poluição, além do impacto para a saúde pública. Diante desse panorama, determina-se a necessidade de abordar a problemática da resistência bacteriana desde a perspectiva de "uma saúde" em que a vigilância tradicional, focada nos níveis humano e veterinário, esteja articulada com a vigilância epidemiológica ambiental, principalmente baseada em águas residuais.

Alta sensibilidad a la mupirocina en aislados de Staphylococcus aureus que colonizan pacientes en hemodiálisis en una unidad renal de Medellín, Colombia / High mupirocin susceptibility in isolates of Staphylococcus aureus colonizing hemodialysis patients in a dialysis unit at Medellín

RESUMEN Objetivo: describir el porcentaje de resistencia a la mupirocina y a otros antibióticos en aislados de Staphylococcus aureus que colonizan pacientes en hemodiálisis. Métodos: estudio descriptivo en el que se incluyeron pacientes en hemodiálisis en una unidad renal de Medellín. La colonización por S. aureus fue evaluada en las fosas nasales y en la piel. La identificación bacteriana se realizó por PCR y la sensibilidad antibiótica se determinó por el sistema automatizado VITEK-2 y por el método E-test. Las características clínicas de los pacientes fueron evaluadas con la historia clínica. Resultados: se incluyeron 210 pacientes, de estos el 50,5 % (n = 106) fueron mujeres, con una mediana para la edad de 62 años (RIC 51,87-71,13). De las características clínicas se destacó el uso frecuente de antibióticos: 59 % (n = 124) y la historia de hospitalización: 69 % (n = 145). El porcentaje de colonización por S. aureus fue de 33,8 % (n = 71) y el sitio más frecuente de colonización fue las fosas nasales (19 %; n = 40). Todos los aislados fueron sensibles a la mupirocina por el método de VITEK-2. Sin embargo, un aislado presentó resistencia de bajo nivel a la mupirocina por E-test. La colonización por aislados resistentes a meticilina (SARM) fue de 4,8 % (n = 10) y estos presentaron, principalmente, resistencia solamente a la oxacilina (58,3 %; n = 7). Conclusión: la alta sensibilidad a la mupirocina en aislados de S. aureus colonizantes sugiere su uso como terapia profiláctica en pacientes en hemodiálisis con alto riesgo de infección. Es importante fortalecer los programas de uso racional de antibióticos para evitar la diseminación de mecanismos de resistencia a estos y a otros en las unidades renales.

SUMMARY Objective: To describe the resistance percentage to mupirocin and other antibiotics in Staphylococcus aureus isolates colonizing hemodialysis patients. Methods: A descriptive study was conducted at an outpatient dialysis center in Medellín and hemodialysis patients with catheter were included. Colonization by S. aureus was evaluated in nostrils and skin. Bacterial identification was performed by PCR and antibiotic susceptibility was determined by the Vitek-2 automated system and by E-test. Clinical information was obtained from medical records. Results: Two hundred and ten patients were included, of which 50.5% (n=106) were women, with a median for the age of 62 years (IQR 51,87-71,13). Among the clinical characteristics, the frequent use of antibiotics 59% (n=124) and the history of hospitalization 69% (n=145) were highlighted. The percentage of colonization by S. aureus was 33.8% (n=71) and the most frequent site of colonization was nostrils (19%; n=40). All isolates were susceptible to mupirocin by the method of Vitek-2. However, one isolate showed low level resistance to mupirocin by E-test. Colonization by methicillinresistant isolates (MRSA) was 4.8% (n=10); which presented mainly resistance only to oxacillin (58,3%; n = 7). Conclusion: The high susceptibility to mupirocin in isolates of colonizing S. aureus suggests its use as prophylactic therapy in hemodialysis patients with high risk of infection. It is important to strengthen programs for the rational use of antibiotics to prevent the spread of mechanisms of resistance to this and other antibiotics at dialysis units.

Knowledge, attitude, and practice regarding antibiotic use and resistance among medical students in Colombia: a cross-sectional descriptive study.

BACKGROUND: This study was designed to describe the knowledge, attitude, and practice regarding antibiotic use and resistance among medical students in Medellín, Colombia. METHODS: A cross-sectional study was conducted among medical students from three universities from September to December 2018. The sample size was calculated, the classrooms were visited, and those students who were willing to participate were invited to do so. The data collection instrument was constructed in three stages: i) the literature was systematically reviewed, ii) the items from the studies identified were extracted, and iii) item reduction was performed with exploratory factor analysis. Data were analyzed by calculating absolute and relative frequencies and means for quantitative variables. The indexes of knowledge, attitude, and practice were transformed to a scale from 0 (worst possible score) to 100. Comparisons were performed using the Mann-Whitney U test, Kruskall-Wallis H test, and linear regressions. RESULTS: Five hundred and thirty-two medical students were included with a response rate of 96%. Of the total participants, 49.1% reported having used antibiotics within the past year. Regarding knowledge, only 18.2% had heard of the term "antimicrobial stewardship" and 69.3% were aware that empiric antibiotic therapy contributes to antibiotic resistance. Regarding attitude, 11.6% considered that antibiotics should be discontinued as soon as symptoms disappear and 24.6% stated that it is better to prescribe broad-spectrum antibiotics to ensure that the patient is cured. Regarding practice, 28.5% recognized that resistance is a multifactorial problem, but they do not act on it because they consider that individual actions would have little impact. The adjusted linear regression showed that the variables associated with knowledge, attitude, and practice were socioeconomic status, training cycle, university, previous experience of research or education, the general perception of the training received, and antibiotic consumption. CONCLUSION: Knowledge, attitude, and practice differ widely depending on the university, training cycle, and socioeconomic status, and a significant proportion of students consider that the standard of training received at the university on antibiotics and bacterial resistance is poor or mediocre. These findings show that there is a need to strengthen the medical students' curriculum on antibiotics, mechanisms of antibiotic resistance, and the prudent use of antibiotics as an important strategy to combat problem-resistant public health, primarily in endemic countries.

Knowledge regarding antibiotic use among students of three medical schools in Medellin, Colombia: a cross-sectional study.

BACKGROUND: The objective of the present study was to describe the knowledge regarding the antibiotic therapy of students of three medical schools in Medellín, Colombia. METHODS: The study population comprised medical students who were enrolled in three universities. The instrument contained questions regarding their current academic term, the university, the perceived quality of the education received on antibiotic therapy and bacterial resistance, and specific questions on upper respiratory tract infections, pneumonia, urinary tract infections, and skin and soft tissue infections. The information was analyzed by calculating frequencies and measures of dispersion and central tendency. Knowledge regarding the treatment for each type of infection was compared using the Mann-Whitney U test and the Kruskal-Wallis H test. RESULTS: We included 536 medical students, of which 43.5% students consider that the university has not sufficiently trained them to interpret antibiograms and 29.6% students consider that the quality of information received on the subject at their university ranges from regular to poor. The mean score for knowledge regarding antibiotic therapy for upper respiratory tract infections was 44.2 (9.9) on a scale from 0 to 100. The median score with regard to the treatment of pneumonia was 52.9 (14.7), that of urinary tract infection was 58.7 (14.8), and that of skin and soft tissue infections was 63.1 (19.4). The knowledge regarding antibiotic therapy for upper respiratory tract infections, pneumonia, and urinary tract infection does not improve with the academic term, the university, or perceived quality of the education received. CONCLUSION: A large proportion of medical students perceive that the training received from the university is insufficient with regard to antibiotic use and bacterial resistance, which is consistent with the limited knowledge reflected in the selection of antibiotic treatment for respiratory, urinary tract, and skin and soft tissue infections. Overall, the situation was identical among all universities, and it did not significantly increase with the completion of an academic term.

Resistencia antimicrobiana en el siglo XXI: ¿hacia una era postantibiótica? / Antimicrobial resistance in the 21st century: towards a post-antibiotic era? / Resistência antimicrobiana no século XXI: rumo a uma era pós-antibiótica?

Resumen Desde el descubrimiento de la penicilina por Alexander Fleming en 1928, inició una era caracterizada por el desarrollo de diferentes grupos de antibióticos que permitieron el tratamiento adecuado de infecciones graves ocasionadas por bacterias que afectaban la población mundial. Sin embargo, de manera casi simultánea al desarrollo de cada clase de antibióticos, se desencadenó la emergencia de bacterias resistentes, debido en parte al uso extendido e inadecuado de estos medicamentos. Como consecuencia, el manejo de las infecciones bacterianas se ha complicado cada vez más y en la actualidad las opciones de tratamiento son pocas, sumado a que el desarrollo de nuevos antimicrobianos ha dejado de ser atractivo para la industria farmacéutica. Esta situación ha conducido a que la Organización Mundial de la Salud advierta sobre la llegada de una era postantibiótica, donde infecciones comunes o anteriormente de fácil tratamiento pueden ocasionar muertes como resultado de la resistencia bacteriana a los diferentes grupos de antibióticos. Por lo anterior, surgen preguntas sobre cómo pudo ser originada esta situación y qué soluciones son necesarias para evitar la temida era, preguntas que tratan de ser respondidas en el presente ensayo, mediante el abordaje de aspectos relacionados no solo con los microorganismos, sino también con contextos sociales, económicos e incluso políticos, que influyen en el aumento de la resistencia antimicrobiana y dificultan su control.

Abstract Alexander Fleming's discovery of penicillin in 1928 marked the beginning of an era characterized by the development of different groups of antibiotics that allowed the proper treatment of serious infections caused by bacteria that affected the world population. However, the development of each class of antibiotics almost simultaneously triggered the emergence of resistant bacteria, due in part to the widespread and inappropriate use of these medicines. As a result, managing bacterial infections has become increasingly complicated and currently there are few treatment options, added to the fact that the development of new antimicrobials is no longer attractive to the pharmaceutical industry. This situation has led the World Health Organization to warn of the arrival of a post-antibiotic era, where common or previously easily treated infections could cause deaths as a result of bacterial resistance to several groups of antibiotics. Therefore, questions arise about how this situation could have come to be and what solutions are needed to avoid the dreaded post-antibiotic era, questions that we attempt to answer in this paper by addressing aspects related not only to microorganisms, but also to social, economic and even political contexts, which influence the increase of antimicrobial resistance and hinder its control.

Resumo Desde a descoberta da penicilina por Alexander Fleming em 1928, iniciou-se uma era caracterizada pelo desenvolvimento de diferentes grupos de antibióticos que permitiram o tratamento adequado de infecções graves causadas por bactérias que afetavam a população mundial. No entanto, quase simultaneamente ao desenvolvimento de cada classe de antibióticos, foi desencadeado o surgimento de bactérias resistentes, devido parcialmente ao uso generalizado e inadequado desses medicamentos. Como consequência, o tratamento de infecções bacterianas tornou-se cada vez mais complicado e atualmente existem poucas opções para fazê-lo, além de que o desenvolvimento de novos antimicrobianos deixou de ser atrativo para a indústria farmacêutica. Essa situação levou a Organização Mundial da Saúde a alertar sobre a chegada de uma era pós-antibiótica, na qual as infecções comuns ou previamente tratadas com facilidade podem causar mortes como resultado da resistência bacteriana a diferentes grupos de antibióticos. Portanto, surgem questões sobre como se originou essa situação e quais soluções são necessárias para evitar a era temida. Este ensaio tenta responder essas questões, abordando aspectos relacionados não apenas aos microrganismos, mas também aos contextos sociais, econômicos e até políticos, que influenciam o aumento da resistência antimicrobiana e dificultam seu controle.

Health-Related Quality of Life in Patients with Chronic Kidney Disease in Hemodialysis in Medellín (Colombia).

PURPOSE: Hemodialysis is a treatment that is essential for the survival of patients with terminal chronic kidney disease. However, it is highly invasive, non-curative, and physically, psychologically, socially, and financially demanding, which has an impact on the patient's health-related quality of life (HRQL). In Colombia, research from the point of view of patients undergoing hemodialysis is scarce. PATIENTS AND METHODS: We conducted a cross-sectional study involving 142 patients undergoing hemodialysis. We used an instrument that included the demographic and clinical information as well as the Charlson Comorbidity Index and Karnofsky Performance Status Scale. HRQL was assessed using EQ-5D-5L and KDQOL-36. The analysis was done using measures of central tendency for quantitative variables and relative frequencies for qualitative variables, in addition bivariate and multivariate regression analyses were conducted. RESULTS: Based on the scores of the EQ-5D-5L scale, it was found that 14.5% subjects showed severe mobility problems, 5.8% were unable to bathe or dress by themselves, 12.9% were unable to perform usual activities, 13.5% were experiencing pain or discomfort (between strong and extreme), and 58.6% showed a certain degree of anxiety or depression. The KDQOL-36 scores were 67.4 ± 19.4 for the symptoms domain and 35.0 ± 27.5 for the disease burden domain. Results of the linear regression analysis showed that the main factors associated with HRQL were the Karnofsky Index and serum albumin levels (p < 0.05). CONCLUSION: The result of this study revealed the impact on the quality of life of Colombian patients undergoing hemodialysis with chronic kidney disease who were highly affected by the disease burden. KDQOL-36 has excellent properties of reliability, internal consistency, and discriminant power; thus, its use is recommended in subsequent studies to monitor HRQL in this population.

Direct medical costs of urinary tract infections by Gram-negative bacilli resistant to beta-lactams in a tertiary care hospital in Medellín, Colombia / Costos médicos directos de las infecciones del tracto urinario por bacilos Gram negativos resistentes a betalactámicos en un hospital de alta complejidad de Medellín, Colombia

Introduction: Urinary tract infections are very frequent in the hospital environment and given the emergence of antimicrobial resistance, they have made care processes more complex and have placed additional pressure on available healthcare resources. Objective: To describe and compare excess direct medical costs of urinary tract infections due to Klebsiella pneumoniae, Enterobacter cloacae and Pseudomonas aeruginosa resistant to beta-lactams. Materials and methods: A cohort study was conducted in a third level hospital in Medellín, Colombia, from October, 2014, to September, 2015. It included patients with urinary tract infections caused by beta-lactam-susceptible bacteria, third and fourth generation cephalosporin-resistant, as well as carbapenem-resistant. Costs were analyzed from the perspective of the health system. Clinical-epidemiological information was obtained from medical records and the costs were calculated using standard tariff manuals. Excess costs were estimated with multivariate analyses. Results: We included 141 patients: 55 (39%) were sensitive to beta-lactams, 54 (38.3%) were resistant to cephalosporins and 32 (22.7%) to carbapenems. The excess total adjusted costs of patients with urinary tract infections due to cephalosporin- and carbapenem-resistant bacteria were US$ 193 (95% confidence interval (CI): US$ -347-734) and US$ 633 (95% CI: US$ -50-1316), respectively, compared to the group of patients with beta-lactam sensitive urinary tract infections. The differences were mainly found in the use of broad-spectrum antibiotics such as meropenem, colistin, and fosfomycin. Conclusion: Our results show a substantial increase in the direct medical costs of patients with urinary tract infections caused by beta-lactam-resistant Gram-negative bacilli (cephalosporins and carbapenems). This situation is of particular concern in endemic countries such as Colombia, where the high frequencies of urinary tract infections and the resistance to beta-lactam antibiotics can generate a greater economic impact on the health sector.

Introducción. Las infecciones del tracto urinario son muy frecuentes en el ámbito hospitalario. Debido a la aparición de la resistencia antimicrobiana, la complejidad de los procesos de atención ha aumentado y, con ello, la demanda de recursos. Objetivo. Describir y comparar el exceso de los costos médicos directos de las infecciones del tracto urinario por Klebsiella pneumoniae, Enterobacter cloacae y Pseudomonas aeruginosa resistentes a betalactámicos. Materiales y métodos. Se llevó a cabo un estudio de cohorte en una institución de tercer nivel de Medellín, Colombia, entre octubre del 2014 y septiembre del 2015. Se incluyeron los pacientes con infección urinaria, unos por bacterias sensibles a los antibióticos betalactámicos, y otros por bacterias resistentes a las cefalosporinas de tercera y cuarta generación y a los antibióticos carbapenémicos. Los costos se analizaron desde la perspectiva del sistema de salud. La información clínico-epidemiológica se obtuvo de las historias clínicas y los costos se calcularon utilizando los manuales tarifarios estándar. El exceso de costos se estimó mediante análisis multivariados. Resultados. Se incluyeron 141 pacientes con infección urinaria: 55 (39 %) por bacterias sensibles a los betalactámicos, 54 (38,3 %) por bacterias resistentes a las cefalosporinas y 32 (22,7 %) por bacterias resistentes a los carbapenémicos. El exceso de costos totales ajustado de los 86 pacientes con infecciones del tracto urinario por bacterias resistentes a las cefalosporinas y a los carbapenémicos, fue de USD$ 193 (IC95% -347 a 734) y USD$ 633 (IC95% -50 a 1.316), respectivamente comparados con el grupo de 55 pacientes por bacterias sensibles a los betalactámicos. Las diferencias se presentaron principalmente en el uso de antibióticos de amplio espectro, como el meropenem, la colistina y la fosfomicina. Conclusión. Los resultados evidenciaron un incremento sustancial de los costos médicos directos de los pacientes con infecciones del tracto urinario por bacterias resistentes a las cefalosporinas o a los carbapenémicos. Esta situación genera especial preocupación en los países endémicos como Colombia, donde la alta frecuencia de infecciones del tracto urinario y de resistencia a los betalactámicos puede causar un mayor impacto económico en el sector de la salud.

Costos médicos directos de las infecciones del tracto urinario por bacilos Gram negativos resistentes a betalactámicos en un hospital de alta complejidad de Medellín, Colombia / Direct medical costs of urinary tract infections by Gram-negative bacilli resistant to beta-lactams in a tertiary care hospital in Medellín, Colombia

Resumen Introducción. Las infecciones del tracto urinario son muy frecuentes en el ámbito hospitalario. Debido a la aparición de la resistencia antimicrobiana, la complejidad de los procesos de atención ha aumentado y, con ello, la demanda de recursos. Objetivo. Describir y comparar el exceso de los costos médicos directos de las infecciones del tracto urinario por Klebsiella pneumoniae, Enterobacter cloacae y Pseudomonas aeruginosa resistentes a betalactámicos. Materiales y métodos. Se llevó a cabo un estudio de cohorte en una institución de tercer nivel de Medellín, Colombia, entre octubre del 2014 y septiembre del 2015. Se incluyeron los pacientes con infección urinaria, unos por bacterias sensibles a los antibióticos betalactámicos, y otros por bacterias resistentes a las cefalosporinas de tercera y cuarta generación y a los antibióticos carbapenémicos. Los costos se analizaron desde la perspectiva del sistema de salud. La información clínico-epidemiológica se obtuvo de las historias clínicas y los costos se calcularon utilizando los manuales tarifarios estándar. El exceso de costos se estimó mediante análisis multivariados. Resultados. Se incluyeron 141 pacientes con infección urinaria: 55 (39 %) por bacterias sensibles a los betalactámicos, 54 (38,3 %) por bacterias resistentes a las cefalosporinas y 32 (22,7 %) por bacterias resistentes a los carbapenémicos. El exceso de costos totales ajustado de los 86 pacientes con infecciones del tracto urinario por bacterias resistentes a las cefalosporinas y a los carbapenémicos, fue de USD$ 193 (IC95% -347 a 734) y USD$ 633 (IC95% -50 a 1.316), respectivamente comparados con el grupo de 55 pacientes por bacterias sensibles a los betalactámicos. Las diferencias se presentaron principalmente en el uso de antibióticos de amplio espectro, como el meropenem, la colistina y la fosfomicina. Conclusión. Los resultados evidenciaron un incremento sustancial de los costos médicos directos de los pacientes con infecciones del tracto urinario por bacterias resistentes a las cefalosporinas o a los carbapenémicos. Esta situación genera especial preocupación en los países endémicos como Colombia, donde la alta frecuencia de infecciones del tracto urinario y de resistencia a los betalactámicos puede causar un mayor impacto económico en el sector de la salud.

Abstract Introduction: Urinary tract infections are very frequent in the hospital environment and given the emergence of antimicrobial resistance, they have made care processes more complex and have placed additional pressure on available healthcare resources. Objective: To describe and compare excess direct medical costs of urinary tract infections due to Klebsiella pneumoniae, Enterobacter cloacae and Pseudomonas aeruginosa resistant to beta-lactams. Materials and methods: A cohort study was conducted in a third level hospital in Medellín, Colombia, from October, 2014, to September, 2015. It included patients with urinary tract infections caused by beta-lactam-susceptible bacteria, third and fourth generation cephalosporin-resistant, as well as carbapenem-resistant. Costs were analyzed from the perspective of the health system. Clinical-epidemiological information was obtained from medical records and the costs were calculated using standard tariff manuals. Excess costs were estimated with multivariate analyses. Results: We included 141 patients: 55 (39%) were sensitive to beta-lactams, 54 (38.3%) were resistant to cephalosporins and 32 (22.7%) to carbapenems. The excess total adjusted costs of patients with urinary tract infections due to cephalosporin- and carbapenem-resistant bacteria were US$ 193 (95% confidence interval (CI): US$ -347-734) and US$ 633 (95% CI: US$ -50-1316), respectively, compared to the group of patients with beta-lactam sensitive urinary tract infections. The differences were mainly found in the use of broad-spectrum antibiotics such as meropenem, colistin, and fosfomycin. Conclusion: Our results show a substantial increase in the direct medical costs of patients with urinary tract infections caused by beta-lactam-resistant Gram-negative bacilli (cephalosporins and carbapenems). This situation is of particular concern in endemic countries such as Colombia, where the high frequencies of urinary tract infections and the resistance to beta-lactam antibiotics can generate a greater economic impact on the health sector.

High excess costs of infections caused by carbapenem-resistant Gram-negative bacilli in an endemic region.

The financial burden of antibiotic resistance is a serious concern worldwide. The aim of this study was to describe the excess costs associated with pneumonia, bacteraemia, surgical site infections and intra-abdominal infections (IAIs) caused by carbapenem-resistant Gram-negative bacilli in Medellín, Colombia, an endemic region for carbapenem resistance. A cohort study was conducted in a third-level hospital from 2014-2015. All patients with carbapenem-resistant and carbapenem-susceptible Gram-negative bacterial infections were included. Pharmaceutical, medical and surgical direct costs were described from the health system perspective. Excess costs were estimated from generalised linear models with gamma distribution and adjusted for variables that could affect the cost difference. A total of 218 patients were enrolled, 48 (22.0%) of whom were infected with carbapenem-resistant bacteria. IAIs were the most frequent. The adjusted total excess cost was US$3966 [95% confidence interval (CI) US$1684-6249], with a significantly higher cost for antibiotics, followed by hospital stay, laboratory tests and interconsultation. The highest excess cost was attributed mainly to the use of broad-spectrum antibiotics (US$1827, 95% CI US$1005-2648), followed by length of hospital stay (US$1015, 95% CI US$163-1867). The results of this study highlight the importance of designing antimicrobial stewardship programmes and infection control strategies in endemic regions to reduce the financial threat of antimicrobial resistance to health systems.

Brotes hospitalarios de bacterias resistentes a colistina: revisión sistemática de la literatura / Outbreaks of colistin resistant bacteria: systematic review

Objetivo: La colistina se ha constituido en un medicamento de uso común en países endémicos en resistencia a carbapenémicos; sin embargo, con su uso ha emergido el reporte de resistencia. El objetivo de este estudio es describir los brotes hospitalarios por bacterias resistentes a colistina Material y método: Revisión sistemática de la literatura en cinco bases de datos siguiendo los criterios de la guía PRISMA de identificación, tamización, elección e inclusión. Resultados: Se identificaron 13 brotes en 7 países diferentes, 77% (n = 10) en Italia y Grecia, y 61,5% (n=8) en cepas de K. pneumoniae. Los pacientes presentaron condiciones de base, con múltiples comorbilidades y exposición afrecuente a los servicios de salud. Las pruebas y los criterios de susceptibilidad fueron variables, los mecanismos de resistencia que se encuentran simultáneamente con resistencia a colistina incluyen carbapenemasas y betalactamasas de espectro extendido. El genotipo predominante de acuerdo a MLST fue el ST-258. Conclusión: La emergencia de resistencia a colistina no se circunscribe a un grupo etario ni a una comorbilidad específica; sin embargo, se concentra en países donde la resistencia a carbapenémicos es endémica. Esto permite alertar a las autoridades sanitarias y a los centros hospitalarios para establecer programas de vigilancia, prevención y control que permiten la detección y contención oportuna de esta problemática

Objetive: Colistin has become a drug commonly used in endemic countries in resistance to carbapenems; however, with their use has emerged the resistance. The objective: of this study is to describe outbreaks by bacteria resistant to colistin Design: Systematic review of the literature in five databases with the criteria guide PRISMA of identification, tamization, election and inclusion. Results: 13 outbreaks were identified in 7 different countries, 77% (n = 10) in Italy and Greece, and 61.5% (n = 8) in K. pneumoniae strains. Patients had baseline conditions, multiple comorbidities and frequent exposure to health services. Tests and susceptibility criteria were variable, the resistance mechanisms that are simultaneously with the resistant to colistin include carbapenemases and extended spectrum beta-lactamases. The predominant genotype according to MLST was the ST-258. Conclusion: The emergence of resistance to colistin is not limited to an age group or a specific comorbidity; however, it concentrated in countries where resistance to carbapenems is endemic. This allows alert health authorities and hospitals to establish programs of surveillance, prevention and control that enable timely detection and containment of this problem

In vitro susceptibility of methicillin-resistant Staphylococcus aureus isolates from skin and soft tissue infections to vancomycin, daptomycin, linezolid and tedizolid

Abstract Introduction Treatment of multidrug-resistant Gram-positive infections caused by Staphylococcus aureus remains as a clinical challenge due to emergence of new resistance mechanisms. Tedizolid is a next-generation oxazolidinone, recently approved for skin and soft tissues infections. We conducted a study to determine in vitro susceptibility to vancomycin, daptomycin, linezolid and tedizolid in MRSA clinical isolates from adult patients with skin and soft tissue infections. Material and methods Methicillin-resistant S. aureus isolates were collected in three tertiary-care hospitals of Medellin, Colombia, from February 2008 to June 2010 as part of a previous study. Clinical characteristics were assessed by medical records and MIC values were determined by Epsilometer test. Genotypic analysis included spa typing, MLST, and SCCmec typing. Results A total of 150 MRSA isolates were evaluated and tedizolid MIC values obtained showed higher in vitro activity than other antimicrobials, with MIC values ranging from 0.13 µg/mL to 0.75 µg/mL and lower values of MIC50 and MIC90 (0.38 µg/mL and 0.5 µg/mL). In contrast, vancomycin and linezolid had higher MIC values, which ranged from 0.5 µg/mL to 2.0 µg/mL and from 0.38 µg/mL to 4.0 µg/mL, respectively. Tedizolid MICs were 2- to 5-fold lower than those of linezolid. Clinical characteristics showed high previous antimicrobial use and hospitalization history. The majority of the strains belong to the CC8 harboring the SCCmec IVc and were associated with the spa t1610 (29.33%, n = 44). Conclusion In vitro effectiveness of tedizolid was superior for isolates from skin and soft tissue infections in comparison with the other antibiotics evaluated. The above added to its less toxicity, good bioavailability, daily dose and unnecessity of dosage adjustment, make tedizolid in a promising alternative for the treatment of infections caused by MRSA.

In vitro susceptibility of methicillin-resistant Staphylococcus aureus isolates from skin and soft tissue infections to vancomycin, daptomycin, linezolid and tedizolid.

INTRODUCTION: Treatment of multidrug-resistant Gram-positive infections caused by Staphylococcus aureus remains as a clinical challenge due to emergence of new resistance mechanisms. Tedizolid is a next-generation oxazolidinone, recently approved for skin and soft tissues infections. We conducted a study to determine in vitro susceptibility to vancomycin, daptomycin, linezolid and tedizolid in MRSA clinical isolates from adult patients with skin and soft tissue infections. MATERIAL AND METHODS: Methicillin-resistant S. aureus isolates were collected in three tertiary-care hospitals of Medellin, Colombia, from February 2008 to June 2010 as part of a previous study. Clinical characteristics were assessed by medical records and MIC values were determined by Epsilometer test. Genotypic analysis included spa typing, MLST, and SCCmec typing. RESULTS: A total of 150 MRSA isolates were evaluated and tedizolid MIC values obtained showed higher in vitro activity than other antimicrobials, with MIC values ranging from 0.13µg/mL to 0.75µg/mL and lower values of MIC50 and MIC90 (0.38µg/mL and 0.5µg/mL). In contrast, vancomycin and linezolid had higher MIC values, which ranged from 0.5µg/mL to 2.0µg/mL and from 0.38µg/mL to 4.0µg/mL, respectively. Tedizolid MICs were 2- to 5-fold lower than those of linezolid. Clinical characteristics showed high previous antimicrobial use and hospitalization history. The majority of the strains belong to the CC8 harboring the SCCmec IVc and were associated with the spa t1610 (29.33%, n=44). CONCLUSION: In vitro effectiveness of tedizolid was superior for isolates from skin and soft tissue infections in comparison with the other antibiotics evaluated. The above added to its less toxicity, good bioavailability, daily dose and unnecessity of dosage adjustment, make tedizolid in a promising alternative for the treatment of infections caused by MRSA.

Diseminación de cepas Staphylococcus aureus sensible a meticilina (SASM) relacionadas genéticamente, pertenecientes al CC45, entre portadores nasales sanos de hogares infantiles de Medellín, Colombia / Spread of genetically related methicillin-susceptible Staphylococcus aureus belonging to CC45, in healthy nasal carriers in Child Day Care Centers of Medellin, Colombia

INTRODUCCIÓN: La colonización por Staphylococcus aureus desempeña un papel importante en la epidemiología y patogénesis de las infecciones que causa. La población infantil es una de las más susceptibles a colonizarse; sin embargo, en Colombia los estudios en comunidad y en población infantil son escasos. OBJETIVO: Determinar la relación clonal de aislamientos colonizantes de S. aureus en menores de 8 hogares infantiles de Medellín y describir las características epidemiológicas presentes en esta población. MÉTODOS: Se realizó un estudio observacional transversal donde se seleccionó una muestra de 200 menores entre los 6 meses y los 5 años de edad, provenientes de 8 hogares infantiles de Medellín, Colombia, durante 2011. Las muestras fueron tomadas de fosas nasales. Los aislamientos de S. aureus y la resistencia a meticilina se confirmaron molecularmente, empleando los genes nuc y mec. La genotipificación incluyó tipificación del SCCmec, tipificación de spa, PFGE y MLST. La información epidemiológica fue obtenida de los padres y analizada en SPSS® 21.0. RESULTADOS: La frecuencia de colonización en los hogares varió entre el 16,7% (n = 3) y el 53,6% (n = 15). En el interior de 4 hogares infantiles se identificaron aislamientos de S. aureus relacionados entre sí. Adicionalmente, el 50% de todos los aislamientos de S. aureus sensible a meticilina se agruparon en 3 clúster, que pertenecían a los complejos clonales CC45, CC30 y CC121. CONCLUSIÓN: La tipificación molecular de los aislamientos de los menores colonizados y el análisis realizado en el interior de los hogares permitió describir la diseminación de las cepas colonizantes en el interior de los hogares infantiles de la ciudad de Medellín, principalmente del CC45, un clon exitoso en colonización

INTRODUCTION: Colonization plays a major role in the epidemiology and pathogenesis of Staphylococcus aureusinfections. The child population is one of the most susceptible to colonization; however, community and children studies are limited in Colombia. OBJECTIVE: To assess the clonal relationship of S. aureus strains isolated from colonized children in eight day care centers (DCCs) from Medellin and to determine the presence of epidemiological characteristics in these populations. METHODS: An observational cross-sectional study was conducted on a sample of 200 children aged from 6 months to 5 years attending eight DCCs in Medellin, Colombia, during 2011. Nasal samples were collected from each nostril. The isolates species and methicillin resistance were molecularly confirmed using nuc and mec genes. Genotypic analysis included SCCmec typing, spa typing, PFGE and MLST. Epidemiological information was obtained from the parents and analyzed using the statistics program SPSS 21.0 RESULTS: The colonization frequency in DCCs ranged from 16.7% (n = 3) to 53.6% (n = 15). Genetically related isolates were identified inside four DCCs. Half (50%) of the isolates were grouped in 3 clusters, which belonged to the clonal complexes CC45, CC30, and CC121. CONCLUSION: Molecular typing of isolates from colonized children and comparison among DCCs showed the spread of colonizing strains inside DCCs in Medellin; predominantly the CC45 clone, a successful child colonizer

[Spread of genetically related methicillin-susceptible Staphylococcus aureus belonging to CC45, in healthy nasal carriers in Child Day Care Centers of Medellin, Colombia]. / Diseminación de cepas Staphylococcus aureus sensible a meticilina (SASM) relacionadas genéticamente, pertenecientes al CC45, entre portadores nasales sanos de hogares infantiles de Medellín, Colombia.

INTRODUCTION: Colonization plays a major role in the epidemiology and pathogenesis of Staphylococcus aureus infections. The child population is one of the most susceptible to colonization; however, community and children studies are limited in Colombia. OBJECTIVE: To assess the clonal relationship of S.aureus strains isolated from colonized children in eight day care centers (DCCs) from Medellin and to determine the presence of epidemiological characteristics in these populations. METHODS: An observational cross-sectional study was conducted on a sample of 200 children aged from 6 months to 5 years attending eight DCCs in Medellin, Colombia, during 2011. Nasal samples were collected from each nostril. The isolates species and methicillin resistance were molecularly confirmed using nuc and mec genes. Genotypic analysis included SCCmec typing, spa typing, PFGE and MLST. Epidemiological information was obtained from the parents and analyzed using the statistics program SPSS 21.0 RESULTS: The colonization frequency in DCCs ranged from 16.7% (n=3) to 53.6% (n=15). Genetically related isolates were identified inside four DCCs. Half (50%) of the isolates were grouped in 3 clusters, which belonged to the clonal complexes CC45, CC30, and CC121. CONCLUSION: Molecular typing of isolates from colonized children and comparison among DCCs showed the spread of colonizing strains inside DCCs in Medellin; predominantly the CC45 clone, a successful child colonizer.

Factores relacionados con la colonización por Staphylococcus aureus / Factors related with colonization by Staphylococcus aureus / Fatores relacionados com a colonização por Staphylococcus aureus

Staphylococcus aureus tiene gran capacidad para colonizar la piel y las mucosas de los seres humanos y de diferentes animales. Varios estudios evidencian el papel de dicha colonización en la patogénesis y la epidemiología de las infecciones causadas por S. aureus. Se ha demostrado que los portadores nasales constituyen una fuente importante de propagación de la bacteria; una amplia proporción de las infecciones estafilocócicas invasivas asociadas al cuidado de la salud son de origen endógeno, y la colonización por cepas de S. aureus resistentes a meticilina (SARM), aún mal entendida, origina mayores complicaciones. La importancia de la colonización se ha definido con más profundidad en ambientes hospitalarios, pero recientemente se han hecho estudios en la comunidad con resultados contradictorios sobre la relación colonización-infección. En esta revisión se presentan algunas características relevantes del proceso de colonización por S. aureus, incluyendo las cepas de SARM, y se consideran los factores humanos y del microorganismo que influyen en él. Asimismo, se hace una revisión de los estudios colombianos al respecto.

Staphylococcus aureus has a particular ability to colonize the skin and mucosae of human beings and different animal species. Several studies have demonstrated the important role of such colonization in the pathogenesis and epidemiology of staphylococcal infections. Nasal carriers have been shown to be an important source for S. aureus spread. Most invasive nosocomial S. aureus infections have been confirmed to have endogenous origin, and colonization with methicillin-resistant (MRSA) strains may have adverse consequences. However, the dynamics of the MRSA carrier state remains poorly understood. Although the clinical significance of S. aureus colonization has been demonstrated mostly in hospitals, recent studies have also investigated it in community settings, with contradictory results concerning the colonization- infection relationship. This review focuses on relevant aspects of the dynamics of colonization by S. aureus. It describes human and microorganism factors involved in the colonization process including MRSA strains. Additionally, a summary is presented on Colombian studies on this subject matter.

Staphylococcus aureus tem grande capacidade para colonizar a pele e as mucosas dos seres humanos e de diferentes animais. Vários estudos evidenciam o papel de dita colonização na patogêneses e a epidemiologia das infecções causadas por S. aureus. Demonstrou- se que os portadores nasales constituem uma fonte importante de propagação da bactéria; uma ampla proporção das infecções estafilocócicas invasivas sócias ao cuidado da saúde são de origem endógena, e a colonização por cepas de S. aureus resistentes a meticilina (SARM), ainda mal entendida, origina maiores complicações. A importância da colonização se definiu com mais profundidade em ambientes hospitalares, mas recentemente se fizeram estudos na comunidade com resultados contraditórios sobre a relação colonização-infecção. Nesta revisão se apresentam algumas características relevantes do processo de colonização por S. aureus, incluindo as cepas de SARM, e se consideram os fatores humanos e do microrganismo que influem nele. Assim mesmo, faz-se uma revisão dos estudos colombianos ao respeito.

Acinetobacter baumannii: importancia clínica, mecanismos de resistencia y diagnóstico / Acinetobacter baumannii: Clinical importance, resistance mechanisms and diagnosis

Acinetobacter baumannii ha emergido como una bacteria de gran importancia clínica. Esta bacteria ha sido relacionada con altos porcentajes de mortalidad y posee una alta capacidad para diseminarse en el ambiente hospitalario. Con el paso del tiempo, Acinetobacter baumannii ha adquirido diferentes mecanismos de resistencia a los antibióticos y en la actualidad se reporta resistencia a carbapenémicos, aminoglicósidos, quinolonas y polimixinas, lo que ha complicado el manejo de las infecciones ocasionadas por esta bacteria. El problema se agrava aún más con las limitaciones en el diagnóstico y la carencia de métodos fenotípicos estandarizados que permitan detectar los mecanismos de resistencia específicos. En Colombia se han descrito altos porcentajes de resistencia a los carbapenémicos, lo que ha limitado las opciones terapéuticas y hace necesario el conocimiento de la epidemiología local para establecer medidas de control más certeras.

Currently Acinetobacter baumannii has become in a microorganisms of great clinical importance. It has an extraordinary capacity to spread in the hospital environment and it has been associated with high mortality rates. Acinetobacter baumannii has acquired different resistance mechanisms to antibiotics with reports resistance to carbapenems, aminoglycosides, quinolones and polymyxins; which has complicated the therapy of the infections caused for this pathogen. The problem is further due to the limitations in the diagnosis and the lack of standardized phenotypic methods to detect specific resistance mechanisms. In Colombia has reported high percentages of resistance to carbapenems, which has reduced therapeutic options. The knowledge of local epidemiology is necessary for establish more assertive control measures.