Caracterización clínica, epidemiológica y microbiológica de bacteriemias producidas por enterobacterias resistentes a carbapenems en un hospital universitario de Córdoba, Argentina / Clinical, epidemiological and microbiological characterization of bacteremia produced by carbapenem-resistant enterobacteria in a university hospital in Córdoba, Argentina

Resumen Introducción: Las enterobacterias son una causa principal de infecciones del torrente sanguíneo y su resistencia antimicrobiana se encuentra en aumento. Esto lleva a un incremento de la morbilidad-mortalidad y de los costos en la salud pública. Las enterobacterias resistentes a carbapenems representan un grave desafío a nivel global ya que existen escasas opciones terapéuticas disponibles. Objetivo: Caracterización clínico/microbiológica de las bacteriemias resistentes a carbapenémicos observadas en un período de 4 años. Material y Método: Estudio retrospectivo, observacional y descriptivo, sobre las bacteriemias por enterobacterias resistentes y sensibles a carbapenems. Resultados: Se analizó un total de 84 pacientes con bacteriemia por enterobacterias resistentes y sensibles a carbapenems. Entre las resistentes, observamos una mayor proporción de: tratamiento antimicrobiano previo, hospitalización en unidad de terapia intensiva (UTI), inicio de la bacteriemia en UTI y antecedentes de β-lactamasas de espectro extendido. Además, se detectó un amplio predominio de Klebsiella pneumoniae productor de KPC y una mortalidad atribuible de 52,4%. Discusión: El estudio posibilitó profundizar el conocimiento de una enfermedad emergente de elevada mortalidad, en vistas al diseño y aplicación de estrategias de control de infecciones y de esquemas de tratamiento efectivos adaptados a la epidemiologia local.

Abstract Background: Enterobacteriaceae are a major cause of bloodstream infections and their antimicrobial resistance continues to increase. This leads to higher morbidity-mortality rates and public health costs. Carbapenem-resistant Enterobacteriaceae represent a serious challenge globally, since there are few therapeutic options available. Aim: Clinical/microbiological characterization of the carbapenem-resistant bacteremia observed over a period of 4 years. Methods: Retrospective, observational and descriptive study about bacteremia caused by carbapenem-resistant and susceptible Enterobacteriaceae. Results: A total of 84 patients with bacteremia including carbapenem-resistant and susceptible Enterobacteriaceae were analyzed. We found that patients infected with carbapenem-resistant strains presented a higher proportion of: previous antibiotic treatment, hospitalization in intensive care unit (ICU), onset of the bacteremia during hospitalization in ICU and previous infection with extended-spectrum-beta-lactamase producing Enterobacteriaceae. Additionally, we observed a predominance of KPC-producing Klebsiella pneumoniae and an attributable mortality rate of 52.4%. Discussion: This study allowed for a better understanding of an emerging problem with high mortality, which in turn is useful for the design and adoption of infection control strategies and effective treatment regimens adapted to our local epidemiology.

[Clinical, epidemiological and microbiological characterization of bacteremia produced by carbapenem-resistant enterobacteria in a university hospital in Córdoba, Argentina]. / Caracterización clínica, epidemiológica y microbiológica de bacteriemias producidas por enterobacterias resistentes a carbapenems en un hospital universitario de Córdoba, Argentina.

BACKGROUND: Enterobacteriaceae are a major cause of bloodstream infections and their antimicrobial resistance continues to increase. This leads to higher morbidity-mortality rates and public health costs. Carbapenem-resistant Enterobacteriaceae represent a serious challenge globally, since there are few therapeutic options available. AIM: Clinical/microbiological characterization of the carbapenem-resistant bacteremia observed over a period of 4 years. METHODS: Retrospective, observational and descriptive study about bacteremia caused by carbapenem-resistant and susceptible Enterobacteriaceae. RESULTS: A total of 84 patients with bacteremia including carbapenem-resistant and susceptible Enterobacteriaceae were analyzed. We found that patients infected with carbapenem-resistant strains presented a higher proportion of: previous antibiotic treatment, hospitalization in intensive care unit (ICU), onset of the bacteremia during hospitalization in ICU and previous infection with extended-spectrum-beta-lactamase producing Enterobacteriaceae. Additionally, we observed a predominance of KPC-producing Klebsiella pneumoniae and an attributable mortality rate of 52.4%. DISCUSSION: This study allowed for a better understanding of an emerging problem with high mortality, which in turn is useful for the design and adoption of infection control strategies and effective treatment regimens adapted to our local epidemiology.

[Nosocomial urinary tract infection: an analysis beyond urinary catheterization]. / Epidemiología de las infecciones urinarias asociadas a catéter y no asociadas a catéter en un hospital universitario de tercer nivel.

INTRODUCTION: Nosocomially acquired urinary tract infections (NAUTI) represent an important public health issue, but its characteristics when they are not catheter associated (CA-UTI) or when they take place outside intensive care units (ICU) are poorly understood. OBJECTIVES: To determine the patients' characteristics, etiology and antimicrobial susceptibility of NAUTI, both CA-UTI and no CA-UTI, in general ward and ICU. METHODS: We conducted a retrospective analytic cross-sectional study, between 2009 and 2013, in a third level universitary hospital. All NAUTI episodes were identified, classifying them as CA-UTI and no CA-UTI. RESULTS: We included 253 episodes of NAUTI, being CA-UTI (60,9%) more frequent than no CA-UTI. A 37,4% of no CA-UTI and 59,7% of CA-UTI were identified in ICU. The most frequently isolated microorganisms were Escherichia coli, Klebsiella pneumoniae and Enterococcus sp. A 19% of extended spectrum betalactamase producing gram negative bacilli were found, without differences between groups. CONCLUSION: Patients's comorbidities, microorganisms associated to NAUTI and its antimicrobial susceptibility were similar in CA-UTI and no CA-UTI, as in general ward and ICU.

Epidemiología de las infecciones urinarias asociadas a catéter y no asociadas a catéter en un hospital universitario de tercer nivel / Nosocomial urinary tract infection: an analysis beyond urinary catheterization

Resumen Introducción: Las infecciones urinarias asociadas a la atención de la salud (ITU-AAS) representan un importante problema sanitario, siendo poco conocidas sus características cuando no están asociadas a cateterización urinaria u ocurren fuera de unidades de cuidados intensivos (UCI). Objetivos: Determinar las características de los pacientes con ITU-AAS, etiología y susceptibilidad antimicrobiana de las mismas, tanto asociadas a catéter (ITU-C) como no asociadas a catéter (ITU-noC), en UCI y en sala general. Materiales y Métodos: Se realizó un estudio analítico retrospectivo de corte transversal entre 2009 y 2013 en un hospital universitario de tercer nivel. Se identificaron todos los episodios de ITU-AAS, diferenciándolas en ITU-C e ITU-noC. Resultados: Se incluyeron 253 episodios de ITU-AAS, siendo más frecuentes las ITU-C (60,9%) respecto a ITU-noC. Un 37,4% de ITU-noC y 59,7% de ITU-C ocurrieron en UCI. Los microorganismos aislados más frecuentemente fueron Escherichia coli, Klebsiella pneumoniae y Enterococcus sp. El 19% de los bacilos gramnegativos fueron productores de β-lactamasa de espectro extendido, siendo su frecuencia similar en ambos grupos. Conclusión: Las co-morbilidades de los pacientes con ITU-AAS, los agentes etiológicos responsables y sus correspondientes espectros de sensibilidad, fueron similares en los grupos de ITU-C e ITU-noC, tanto en sala general como en UCI.

Introduction: Nosocomially acquired urinary tract infections (NAUTI) represent an important public health issue, but its characteristics when they are not catheter associated (CA-UTI) or when they take place outside intensive care units (ICU) are poorly understood. Objectives: To determine the patients' characteristics, etiology and antimicrobial susceptibility of NAUTI, both CA-UTI and no CA-UTI, in general ward and ICU. Methods: We conducted a retrospective analytic cross-sectional study, between 2009 and 2013, in a third level universitary hospital. All NAUTI episodes were identified, classifying them as CA-UTI and no CA-UTI. Results: We included 253 episodes of NAUTI, being CA-UTI (60,9%) more frequent than no CA-UTI. A 37,4% of no CA-UTI and 59,7% of CA-UTI were identified in ICU. The most frequently isolated microorganisms were Escherichia coli, Klebsiella pneumoniae and Enterococcus sp. A 19% of extended spectrum betalactamase producing gram negative bacilli were found, without differences between groups. Conclusion: Patients's comorbidities, microorganisms associated to NAUTI and its antimicrobial susceptibility were similar in CA-UTI and no CA-UTI, as in general ward and ICU.

[Uncomplicated urinary tract infection in women: etiology and antimicrobial resistance]. / Infección urinaria no complicada en mujeres: etiología y resistencia a antimicrobianos.

Our objectives were to determine the etiology and analyze the antibiotic resistance profiles of microorganisms causing uncomplicated urinary tract infections in our setting. An analytical cross-sectional study was conducted. In vitro antimicrobial resistance of urine cultures was analyzed. 580 urine cultures of women over age fifteen were included. 82.6 % of urine cultures corresponded to cystitis and the remaining 17.4 % corresponded to pyelonephritis. 353 urine cultures of women <50 years old (60.9%) and 227 of women = 50 years old (39.1%) were obtained. The most common pathogens were Escherichia coli (85.5 %) and Klebsiella pneumoniae (4.7 %). For Escherichia coli, there was a resistance of 28.6% to trimethoprim-sulfamethoxazole,7.9% to ciprofloxacin and 0.4% to nitrofurantoin. Significant difference (p = 0.005) was seen in the resistance to ciprofloxacin in women = 50 years old. Our data show there is a low in vitro resistance to nitrofurantoin

Nuestros objetivos fueron determinar la etiología y analizar los perfiles de resistencia antimicrobiana de los microorganismos causantes de infecciones urinarias no complicadas en nuestro medio. Se realizó un estudio analítico de corte transversal. Se analizó la resistencia antimicrobiana in vitro de los urocultivos. Se incluyeron 580 urocultivos de mujeres mayores de 15 años. Un 82.6% de urocultivos correspondieron a cistitis y el 17.4% a pielonefritis.Se obtuvieron 353 urocultivos de mujeres < 50 años (60.9%) y 227 a ? 50 años (39.1%).Los patógenos más frecuentes fueron: Escherichia coli (85.5%) y Klebsiella pneumoniae (4.7%). Se encontró una resistencia de E coli a trimetoprima-sulfametoxazol del 28.6%, a ciprofloxacina de 7.9% y a nitrofurantoína de 0.4%. Se evidenció diferencia significativa (p=0.005) en la resistencia de E coli a ciprofloxacina en las mujeres ?50 años de edad. Nuestros datos muestran que existe una baja resistencia in vitro a nitrofurantoína.

[Predictive ability of clinical parameters of bacteremia in hemodialysed patients]. / Capacidad predictiva de los parámetros clínico de bacteriemia en pacientes hemodializados.

BACKGROUND: No clinical events to differentiate bacteteremia from other pathologies in hemodialysis patients therefore the physicians makes diagnosis and treatment decisions based on clinical evidence an local epidemiology. OBJECTIVE: the aim of this work was to study the frequency of microorganism isolated from blood culture of hemodialysis patients with suspected bacteraemia and evaluate Sensitivity (S) and Specificity (E) of medical diagnostic orientation in this cases of suspected Materials and methods: we performed an observational and prospective study for one year in hemodialysis patient with suspected bacteremia. We evaluated blood pressure, temperature (Tº), altered conscious state (AEC), respiratory frequency (FR), chills (ESC),diarrhea (DIARR), blood culture results and microbiological identification. We work with the mean ± standar desviation for continuous variables and frequencies for categorical variables We analyzed S, E, negative predictive value (VPN), positive predictive value (VPP) RESULTADOS: a total of 87 events with suspected bacteremia 34 (39%) were confirmed with positive blood culture the most common microorganisms were cocci Gram positive (CGP) 65%, Most relevant clinical variables were PCP ≥ 2 (VPN 81%), Tº ≥ 38 (VPN 76%) and AEC (E 98% y VPP 80%). CONCLUSIONS: CGP were the most prevalent microorganisms None of the clinical variables shows high S and E indicating low usefulness as a predictive tool of bacteremia Excepting AEC with E98% and VPP 80% but it would be necessary to evaluate this variable with a more number patient. Results justify to routine HC use like diagnostic tool.

Predictibilidad de la propagación espacial y temporal de la epidemia de influenza A H1N1 en la Argentina por el método de percolación

La epidemia de influenza A H1N1 se expandió rápidamente a nivel mundial dadas las actuales condiciones de alta interconectividad y velocidad de los transportes, imperantes tanto entre las personas como entre los países y las regiones. La diseminación espacial de la epidemia puede ser explicada mediante la teoría de la percolación, que permite estimar un umbral más allá del cual se produce el traspaso de la epidemia entre distintas regiones geográficas. El objetivo de este trabajo fue probar la capacidad predictiva del modelo de percolación aplicado al análisis de la epidemia de influenza A H1N1 registrada en la Argentina en 2009, de acuerdo a los datos relevados por el Ministerio de Salud Pública de la Nación. Para aplicar el mencionado modelo se consideró al país como un conjunto de figuras geométricas irregulares, contiguas y continuas, que pueden representarse en dos dimensiones en una carta geográfica plana. Se analizó la proporción de provincias infectadas en el momento de la percolación con respecto al tiempo y se compararon los valores observados con los esperados mediante ecuaciones de estimación curvilínea en un modelo logístico. La percolación ocurrió en el día 45. El valor esperado que generó el modelo fue de 42,4 días, intervalo de confianza de 95 % 28,5-56,3. La diferencia entre el valor observado y el esperado arrojó un valor de p = 0,997. Se concluye que el modelo posee un buen ajuste y una adecuada capacidad predictiva.

Spatial and temporal spread predictability of influenza A H1N1 epidemic in Argentina by the percolation method. The influenza A H1N1 epidemic has spread rapidly worldwide on account of the current conditions of high interconnectivity and transport speed both among people and countries. The spatial spread of the epidemics can be explained by the percolation theory which allows to estimate a threshold beyond which the transmission of the infection among different geographic regions occurs. The aim of this study was to test the predictive ability of the percolation model of influenza A H1N1 epidemic in Argentina according to data gathered by the National Department of Public Health. In the model, the country was considered as a set of irregular, contiguous and continuous geometric figures, which can be represented in two dimensions on a plane. We analyzed the proportion of infected provinces at the moment of percolation in relation to time in days and compared observed and expected values by curvilinear equations in a logistic model. Percolation occurred on day 45. The expected value generated by the model was 42.4 days, 95 % CI 28.5 to 56.3. The difference between observed and expected values was p = 0.997. We conclude that the model has good fit and predictive capacity.

Heterogeneous vancomycin-intermediate susceptibility in a community-associated methicillin-resistant Staphylococcus aureus epidemic clone, in a case of Infective Endocarditis in Argentina.

BACKGROUND: Community-Associated Methicillin Resistant Staphylococcus aureus (CA-MRSA) has traditionally been related to skin and soft tissue infections in healthy young patients. However, it has now emerged as responsible for severe infections worldwide, for which vancomycin is one of the mainstays of treatment. Infective endocarditis (IE) due to CA-MRSA with heterogeneous vancomycin-intermediate susceptibility-(h-VISA) has been recently reported, associated to an epidemic USA 300 CA-MRSA clone. CASE PRESENTATION: We describe the occurrence of h-VISA phenotype in a case of IE caused by a strain belonging to an epidemic CA-MRSA clone, distinct from USA300, for the first time in Argentina. The isolate h-VISA (SaB2) was recovered from a patient with persistent bacteraemia after a 7-day therapy with vancomycin, which evolved to fatal case of IE complicated with brain abscesses. The initial isolate-(SaB1) was fully vancomycin susceptible (VSSA). Although MRSA SaB2 was vancomycin susceptible (≤ 2 µg/ml) by MIC (agar and broth dilution, E-test and VITEK 2), a slight increase of MIC values between SaB1 and SaB2 isolates was detected by the four MIC methods, particularly for teicoplanin. Moreover, Sab2 was classified as h-VISA by three different screening methods [MHA5T-screening agar, Macromethod-E-test-(MET) and by GRD E-test] and confirmed by population analysis profile-(PAP). In addition, a significant increase in cell-wall thickness was revealed for SaB2 by electron microscopy. Molecular typing showed that both strains, SaB1 and SaB2, belonged to ST5 lineage, carried SCCmecIV, lacked Panton-Valentine leukocidin-(PVL) genes and had indistinguishable PFGE patterns (subtype I2), thereby confirming their isogenic nature. In addition, they were clonally related to the epidemic CA-MRSA clone (pulsotype I) detected in our country. CONCLUSIONS: This report demonstrates the ability of this epidemic CA-MRSA clone, disseminated in some regions of Argentina, to produce severe and rapidly fatal infections such as IE, in addition to its ability to acquire low-level vancomycin resistance; for these reasons, it constitutes a new challenge for the Healthcare System of this country.

[Spatial and temporal spread predictability of influenza A H1N1 epidemic in Argentina by the percolation method]. / Predictibilidad de la propagación espacial y temporal de la epidemia de influenza A H1N1 en la Argentina por el método de percolación.

The influenza A H1N1 epidemic has spread rapidly worldwide on account of the current conditions of high interconnectivity and transport speed both among people and countries. The spatial spread of the epidemics can be explained by the percolation theory which allows to estimate a threshold beyond which the transmission of the infection among different geographic regions occurs. The aim of this study was to test the predictive ability of the percolation model of influenza A H1N1 epidemic in Argentina according to data gathered by the National Department of Public Health. In the model, the country was considered as a set of irregular, contiguous and continuous geometric figures, which can be represented in two dimensions on a plane. We analyzed the proportion of infected provinces at the moment of percolation in relation to time in days and compared observed and expected values by curvilinear equations in a logistic model. Percolation occurred on day 45. The expected value generated by the model was 42.4 days, 95 % CI 28.5 to 56.3. The difference between observed and expected values was p = 0.997. We conclude that the model has good fit and predictive capacity.

[Use of the fluorescent in situ hybridization technique for the rapid identification of staphylococcus aureus in blood cultures]. / Uso de la técnica de hibridación fluorescente in situ para la identificación rápida de staphylococcus aureus en hemocultivos.

BACKGROUND: The technique of reference for the detection of bacteriemia is the blood culture. One of the most frequent bacteria responsible of bacteriemia is Staphylococcus aureus (SAU). The presence of Gram positive cocci (CGPR), in blood culture give the suspicious of bacteriemia, although the relevance of the finding depends on the correct identification of the microorganism. The definitive typification it demands from 24 to 48 hours. The technique of fluorescent in situ hybridization (FISH), is a rapid method for the identification of bacteria in blood culture. AIMS: The aims of this work was to establish the FISH technique directed to the 16S RNA of SAU in samples of blood cultures with CGPR to the Gram staining, to determine the concordance with the method of reference, and to evaluate the possibility to use as standard method in the laboratory of microbiology. MATERIAL AND METHODS: The blood cultures analyzed in the Laboratory of Microbiology of the Hospital Privado Cordoba from 01.01.2009 to 31.12.09 were included in this study. To each positive blood culture which showed CGPR was applied simultaneously biochemical identification and FISH. RESULTS: From 496 positive samples, 32 showed CGPR, 24 of them were identified as SAU. A concordance of 100% (IC95% 99 to 100) between both methods of diagnosis, with a value of k<0.01 was observed. DISCUSSION: The excellent concordance opens the prospect for a study in order to determine the predictive value of FISH, its sensibility and specificity. Furthermore, it will be possible to evaluate its clinical impact being incorporated in a laboratory of clinical bacteriology.

[Group B streptococcus colonization during pregnancy and prevention of early onset of disease]. / Colonizacion por estreptococo beta hemolitico del grupo B durante el embarazo y prevencion de enfermedad neonatal.

Group B Streptococcus (GBS) is the most frequent cause of early onset of neonatal sepsis. Case-fatality rate is 6-20% for newborns. Neurological sequel occurs in 30% of survivors. In 1996, the Centers for Disease Control and Prevention (CDC), the American College of Obstetricians and Gynecologists, and the American Academy of Pediatrics recommended that obstetrics providers should adopt either a culture-based or a risk-based approach for the prevention of this disease. The aim of this prospective study was to determine the colonization rate of GBS in our population of pregnant women between July 1st 2001 and December 31st 2002, and to introduce a culture-based strategy to prevent early onset neonatal GBS disease. From a population of 1756 pregnant women, 1228 were screened with rectal and vaginal swabs (69.9%). Maternal colonization rate was 1.4% (17 patients). There was one case of early-onset neonatal sepsis consistent with GBS disease (0.6%) in a patient with negative cultures. From the colonized patients, only one presented risk factors. Because most of the colonized women did not present intrapartum risk factors, the results of this study suggest that the culture-based approach should be used for the prevention of early-onset GBS disease in our population. Cost-benefit studies are needed in our country to determine if this prevention strategy is able to be implemented in all the settings of Argentina.

Colonizacion por estreptococo beta hemolitico del grupo B durante el embarazo y prevencion de enfermedad neonatal. / [Group B streptococcus colonization during pregnancy and prevention of early onset of disease]

Group B Streptococcus (GBS) is the most frequent cause of early onset of neonatal sepsis. Case-fatality rate is 6-20

for newborns. Neurological sequel occurs in 30

of survivors. In 1996, the Centers for Disease Control and Prevention (CDC), the American College of Obstetricians and Gynecologists, and the American Academy of Pediatrics recommended that obstetrics providers should adopt either a culture-based or a risk-based approach for the prevention of this disease. The aim of this prospective study was to determine the colonization rate of GBS in our population of pregnant women between July 1st 2001 and December 31st 2002, and to introduce a culture-based strategy to prevent early onset neonatal GBS disease. From a population of 1756 pregnant women, 1228 were screened with rectal and vaginal swabs (69.9

). Maternal colonization rate was 1.4

(17 patients). There was one case of early-onset neonatal sepsis consistent with GBS disease (0.6

) in a patient with negative cultures. From the colonized patients, only one presented risk factors. Because most of the colonized women did not present intrapartum risk factors, the results of this study suggest that the culture-based approach should be used for the prevention of early-onset GBS disease in our population. Cost-benefit studies are needed in our country to determine if this prevention strategy is able to be implemented in all the settings of Argentina.