Update of antimicrobial resistance in level III and IV health institutions in Colombia between January 2018 and December 2021 / Actualización sobre la resistencia antimicrobiana en instituciones de salud de nivel III y IV en Colombia entre enero del 2018 y diciembre del 2021

Introduction: Antimicrobial resistance surveillance is a fundamental tool for the development, improvement, and adjustment of antimicrobial stewardship programs, therapeutic guidelines, and universal precautions to limit the cross-transmission of resistant bacteria between patients. Since the beginning of 2020, the SARS-CoV-2 pandemic profoundly challenged the health system and, according to some reports, increased the rates of antimicrobial resistance. Objective: To describe the behavior of antimicrobial resistance of the most frequent bacterial pathogens in twenty Colombian hospitals from January 2018 to December 2021. Materials and methods: We conducted a descriptive study based on the microbiological information recorded from January 2018 to December 2021 in twenty levels III and IV health institutions in twelve Colombian cities. We identified the species of the ten most frequent bacteria along with their resistance profile to the antibiotic markers after analyzing the data through WHONET. Results: We found no statistically significant changes in most pathogens' resistance profiles from January 2018 to December 2021. Only Pseudomonas aeruginosa had a statistically significant increase in its resistance profile, particularly to piperacillin/tazobactam and carbapenems. Conclusions: The changes in antimicrobial resistance in these four years were not statistically significant except for P. aeruginosa to piperacillin/tazobactam and carbapenems.

Introducción: El comportamiento de la resistencia antimicrobiana es fundamental en el mejoramiento y ajuste de los programas de optimización de uso de antimicrobianos, la implementación de las guías terapéuticas y las precauciones que limitan la transmisión cruzada de bacterias resistentes entre pacientes. Desde el inicio del 2020, la pandemia del SARS-CoV-2 desafió profundamente al sistema de salud y, según algunos reportes, aumentó las tasas de resistencia antimicrobiana. OBJETIVO: Describir el comportamiento de la resistencia antimicrobiana en los microrganismos más frecuentes en veinte hospitales colombianos durante el periodo 2018-2021. Materiales y métodos: Se trata de un estudio descriptivo basado en la información microbiológica reportada por veinte instituciones de salud de nivel III y IV, entre enero de 2018 y diciembre de 2021, en doce ciudades de Colombia, las cuales hacen parte del "Grupo para el estudio de la resistencia nosocomial en Colombia", liderado por la Universidad El Bosque. La identificación de género y especie de los microorganismos más frecuentes, junto con su perfil de resistencia frente a antibióticos marcadores, se determinaron mediante el análisis de los datos vía WHONET. RESULTADOS: En general, los 10 microorganismos más frecuentes analizados a lo largo de los 4 años no presentaron cambios estadísticamente significativos en sus perfiles de resistencia durante los cuatro años del periodo evaluado, de 2018 a 2021. En contraste, Pseudomonas aeruginosa aumentó su resistencia frente a piperacilina-tazobactam y carbapenémicos, lo cual fue estadísticamente significativo. CONCLUSIONES: Los cambios en la resistencia antimicrobiana en estos años no han sido estadísticamente significativos, excepto para P. aeruginosa, bacteria que mostró un incremento en las tasas de resistencia a piperacilina-tazobactam y carbapenémicos.

Antimicrobial Stewardship Programs in Latin America and the Caribbean: A Story of Perseverance, Challenges, and Goals.

Antimicrobial resistance is one of the major global health threats. Antimicrobial stewardship (AMS) has been set as a priority within international action plans to combat this issue. The region of Latin America and the Caribbean are recognized for their high antimicrobial resistance rates; nevertheless, a low number of studies describing implemented interventions for this topic have been published. This review aims to provide an overview of the status of AMS in our region, focusing on the main progress achieved and describing the different published efforts made by countries towards the implementation of antimicrobial stewardship programs (ASP). Common areas of intervention included were (a) education approaches, (b) antimicrobial guideline implementation and monitoring, (c) diagnostic stewardship, (d) technological tools: electronic clinical decision support systems in AMS, (e) pharmacy-driven protocols and collaborative practice agreements, and (f) economic impact. The search demonstrated the varied interventions implemented in diverse healthcare settings; the results accentuate their influence on antimicrobial consumption, antimicrobial resistance, clinical outcomes, and direct economic impact. The integration of multiple strategies within each hospital was highlighted as an essential key to ASP success. Even though the literature found demonstrated clear progress, there is still a special need for strengthening leadership from the top down, defining goals based on needs, and gaining support through policy and financing in LAC.

Antimicrobial stewardship programs in seven Latin American countries: facing the challenges.

BACKGROUND: Studies have shown that more than 50% of the antibiotics used in hospitals are unnecessary or inappropriate and, that antimicrobial resistance may cost up to 20 billion USD in excess medical costs each year. On the other hand, Antimicrobial Stewardship Programs (ASP) significantly reduce inappropriate antimicrobial use, emergence of antimicrobial resistance, healthcare associated infections, and costs in hospital settings. OBJECTIVE: To evaluate the development of ASP and antibiotic savings in 7 Latin American hospitals using standardized quantitative indicators in all the participating health care institutions. METHODS: An interventional study was conducted, where pre- and post- evaluations were performed using a standardized score tool adapted from the Joint Commission International accreditation standards and, the Colombian Institute of Technical Standards and Certification. We evaluated ASP from 7 Latin American hospitals between 2019 and 2020. A pre-intervention evaluation was done in each hospital to quantify the degree of development of the ASP (ASP Development score). Based on these results, tailored on-site training was implemented in each hospital, followed by a post-intervention evaluation to quantify improvement of ASP-development indicators. In addition, monetary savings in antimicrobials derived from the ASP intervention were estimated. RESULTS: In the pre-intervention evaluation, the average ASP development score for the 7 institutions was 65.8% (40-94.3%). The items with the lowest development score were those related to monitoring and communicating the ASP progress and success. For the post-intervention evaluation, 2 institutions couldn't participate due to the pressure imposed by the COVID-19 pandemic. For the remaining 5/7 hospitals, the average ASP development score was 82.3% with an increase of 12.0% when compared to the pre-intervention measurement of the same institutions (average pre-intervention score 70.3% (48.2%-94.3%) The items with a significant increase were key performance indicators, AMS education and training of the prescribers. Three of the seven (3/7) hospitals reported antibiotic monetary savings associated to the ASP intervention. CONCLUSIONS: The use of the tool described shown to be useful to evaluate specific areas of ASP-development that were lacking and tailor interventions for the participating hospitals, consequently, it helped improve ASP-development in the institutions that underwent pre- intervention and post-intervention analysis. In addition, the strategies showed monetary savings on antimicrobial costs when measured.

Molecular mechanisms leading to ceftolozane/tazobactam resistance in clinical isolates of Pseudomonas aeruginosa from five Latin American countries.

Objectives: Identify molecular mechanisms responsible for the in vitro non-susceptibility to ceftolozane/tazobactam (TOL) in a group of 158 clinical isolates of Pseudomonas aeruginosa from five Latin American countries collected before the introduction of TOL into the clinical practice. Methods: Clinical isolates of P. aeruginosa (n = 504) were collected between January 2016 and October 2017 from 20 hospitals located in Argentina, Brazil, Chile, Colombia, and Mexico. Minimum inhibitory concentrations (MICs) to TOL were determined by standard broth microdilution and interpreted according to CLSI breakpoints. Initially, production of carbapenemases in TOL non-susceptible isolates was assessed by Rapidec® followed by qPCR to detect bla KPC, bla NDM-1, bla VIM, and bla IMP. Illumina® WGS was performed for isolates in which non-susceptibility to TOL was not mediated by carbapenemases. Results: A total of 158 (31.3%) isolates were non-susceptible to TOL. In 74 (46.8%) of these isolates, non-susceptibility to TOL was explained by the production of at least one carbapenemase. WGS revealed that some isolates carried ESBLs, mutated bla PDC and ampD, associated with decreased susceptibility to TOL. Conclusion: Substitutions found in PDC and carbapenemase production were the most common presumed mechanisms of resistance to TOL detected in this study. This study shows that epidemiological surveillance is warranted to monitor the emergence of novel mechanisms of resistance to TOL that might compromise its clinical utility.

Molecular Analysis of Polymyxin Resistance among Carbapenemase-Producing Klebsiella pneumoniae in Colombia.

Polymyxin resistance in Klebsiella pneumoniae has been attributed to mutations in mgrB, phoPQ, pmrAB, and crrAB and to the presence of mcr plasmid-mediated genes. Herein, we describe the molecular characteristics of 24 polymyxin- and carbapenem-resistant K. pneumoniae isolates recovered from six Colombian cities between 2009 and 2019. Minimum inhibitory concentrations (MICs) to polymyxin were confirmed by broth microdilution, and whole-genome sequencing was performed to determine sequence type, resistome, and mutations in the genes related to polymyxin resistance, as well the presence of mcr. The results showed high-level resistance to polymyxin (MICs ≥ 4 µg/mL). blaKPC-3 was present in the majority of isolates (17/24; 71%), followed by blaKPC-2 (6/24; 25%) and blaNDM-1 (1/24; 4%). Most isolates belonged to the CG258 (17/24; 71%) and presented amino acid substitutions in PmrB (22/24; 92%) and CrrB (15/24; 63%); mutations in mgrB occurred in only five isolates (21%). Additional mutations in pmrA, crrA, and phoPQ nor any of the mcr resistance genes were identified. In conclusion, we found clonal dissemination of polymyxin and carbapenem-resistant K. pneumoniae isolates in Colombia, mainly associated with CG258 and blaKPC-3. Surveillance of this multidrug-resistant clone is warranted due to the limited therapeutic options for the treatment of carbapenem-resistant K. pneumoniae infections.

Genomic Analysis of CTX-M-Group-1-Producing Extraintestinal Pathogenic E. coli (ExPEc) from Patients with Urinary Tract Infections (UTI) from Colombia.

BACKGROUND: The dissemination of the uropathogenic O25b-ST131 Escherichia coli clone constitutes a threat to public health. We aimed to determine the circulation of E. coli strains belonging to O25b:H4-B2-ST131 and the H30-Rx epidemic subclone causing hospital and community-acquired urinary tract infections (UTI) in Colombia. METHODS: Twenty-six nonduplicate, CTX-M group-1-producing isolates causing UTI in the hospital and community were selected for this study. RESULTS: Twenty-two E. coli isolates harboring CTX-M-15, one CTX-M-3, and three CTX-M-55 were identified. Multilocus Sequence Typing (MLST) showed a variety of sequence types (STs), among which, ST131, ST405, and ST648 were reported as epidemic clones. All the E. coli ST131 sequences carried CTX-M-15, from which 80% belonged to the O25b:H4-B2 and H30-Rx pandemic subclones and were associated with virulence factors iss, iha, and sat. E. coli isolates (23/26) were resistant to ciprofloxacin and associated with amino acid substitutions in quinolone resistance-determining regions (QRDR). We detected two carbapenem-resistant E. coli isolates, one coproducing CTX-M-15, KPC-2, and NDM-1 while the other presented mutations in ompC. Additionally, one isolate harbored the gene mcr-1. CONCLUSIONS: Our study revealed the circulation of the E. coli ST131, O25b:H4-B2-H30-Rx subclone, harboring CTX-M-15, QRDR mutations, and other resistant genes. The association of the H30-Rx subclone with sepsis and rapid dissemination warrants attention from the public health and infections control.

Evaluation of Allplex™ Entero-DR assay for detection of antimicrobial resistance determinants from bacterial cultures.

OBJECTIVE: To evaluate the sensitivity and specificity of the Allplex™ Entero-DR, a quantitative PCR-based method, for the detection of ß-lactamase-encoding genes and vancomycin-resistance determinants in 156 previously characterized Gram-negative bacilli and Enterococcus spp. from bacterial cultures. RESULT: The method had 100% sensitivity and between 92 and 100% of specificity for identifying blaKPC, blaVIM, blaIMP, blaNDM, blaOXA-48-like, blaCTX-M and vanA. In nine isolates, unspecific amplifications were detected. The Ct of these false positives was above 33. The Ct of the correctly identified bla and van genes did not surpass 28 and 30, respectively. None of the clinical isolates included as negative controls yielded any amplification. Therefore, the Allplex™ Entero-DR assay is a highly accurate test for the detection of important antibiotic resistance determinants. With this assay, reliable results can be obtained within 3 h. However, according to our data, samples with Ct values greater than 33 should be considered with caution.

In Vitro Susceptibility to Ceftazidime/Avibactam and Comparators in Clinical Isolates of Enterobacterales from Five Latin American Countries.

Background: High rates of resistance to third-generation cephalosporins and carbapenems in Enterobacterales have been reported in Latin America. Ceftazidime/avibactam (CZA) is the combination of a third-generation cephalosporin and a non-ß-lactam ß-lactamase inhibitor, which has shown activity against isolates producing class A, C and D ß-lactamases. Herein, we evaluated the activity of CZA and comparators against clinical isolates of Enterobacterales in Latin America. Methods: The activity of CZA and comparators was evaluated against clinical isolates of Enterobacterales from Argentina, Brazil, Chile, Colombia and Mexico that were collected between January 2016 and October 2017. One specific phenotypic subset was evaluated. A carbapenem non-susceptible (CNS) phenotype was defined as any isolate displaying a minimum inhibitory concentration (MIC) ≥1 mg/L for ertapenem. Results: CZA was active against 95.8% of all isolates and 77.5% of CNS isolates. Fosfomycin (FOS) and tigecycline (TGC) were the second most active antibiotics with 93.4% of Enterobacterales being susceptible. Conclusions: The results of this study underline the potential therapeutic role of CZA in Latin America.

Performance of disk diffusion and broth microdilution for fosfomycin susceptibility testing of multidrug-resistant clinical isolates of Enterobacterales and Pseudomonas aeruginosa.

OBJECTIVES: This study aimed to evaluate the susceptibility of clinical isolates of Enterobacterales and Pseudomonas aeruginosa to fosfomycin and to determine the concordance of disk diffusion (DD) and broth microdilution (BMD) with agar dilution (AD) for fosfomycin susceptibility testing. METHODS: The activity of fosfomycin against 225 clinical isolates of Escherichia coli (n = 64), Klebsiella pneumoniae (n = 68), Enterobacter spp. (n = 28) and P. aeruginosa (n = 65) was tested by AD, DD and BMD. For DD, results were recorded considering and not considering colonies growing within the inhibition halo as recommended by the CLSI and EUCAST, respectively. Escherichia coli breakpoints were used for all Enterobacterales. Results were reported as categorical agreement (CA), major error (ME; false-resistant), very major error (VME; false-susceptible) and minor error (any other discrepancies). RESULTS: Fosfomycin susceptibility of all tested species was >90% by AD. Following CLSI guidelines, DD was the only method reaching ≥90% CA with AD for E. coli and K. pneumoniae, albeit yielding 6% ME. Neither DD nor BMD achieved acceptable CA percentages for Enterobacter spp. Following EUCAST guidelines, none of the methods had CA ≥ 90%. For Enterobacterales, the best performance of DD is achieved when read as indicated by EUCAST but interpreted according the CLSI breakpoints (>97% CA; 0% VME; ≤2% ME). For P. aeruginosa, BMD yielded the best results (89% CA; 0% VME; 11% ME). CONCLUSION: Neither DD or BMD provide accurate results owing to unacceptable ME and VME percentages even when performed as intended by the guidelines.

Epidemiology of Candida isolates from Intensive Care Units in Colombia from 2010 to 2013 / Epidemiología de aislamientos de Candida en unidades de cuidados intensivos en Colombia durante el período 2010-2013

Background. The frequency of Candida isolates as a cause of hospital infections has risen in recent years, leading to high rates of morbidity and mortality. The knowledge of the epidemiology of those hospital acquired fungal infections is essential to implement an adequate antifungal therapy. Aims. To describe the epidemiology of Candida infections in Intensive Care Units (ICUs) from a surveillance network in Colombia. Methods. Information was collected from the microbiology laboratories of 20 tertiary healthcare institutions from 10 Colombian cities using the Whonet® software version 5.6. A general descriptive analysis of Candida species and susceptibility profiles focusing on fluconazole and voriconazole was completed between 2010 and 2013, including a sub-analysis of healthcare associated infections (HAIs) during the last year. Results. Candida isolates made up 94.5% of the 2680 fungal isolates considered, with similar proportions for Candida albicans and non-C. albicans Candida species (48.3% and 51.7%, respectively). Among the latter, Candida tropicalis (38.6%) and Candida parapsilosis (28.5%) were the most frequent species. Of note, among the blood isolates C. albicans was not the main species. Most of the species isolated were susceptible to fluconazole and voriconazole. From the HAIs reported, 25.5% were caused by Candida; central line-associated bloodstream infection was the most common HAI (58.8%). There were no statistically significant differences regarding length of hospital stay and device days among HAIs. Conclusions. In ICUs of Colombia, non-C. albicans Candida species are as frequent as C. albicans, except in blood samples where non-C. albicans Candida isolates predominate. Further studies are needed to evaluate Candida associated risk factors and to determine its clinical impact (AU)

Antecedentes. La frecuencia de aislamientos de Candida causantes de infecciones hospitalarias ha aumentado en los últimos años, lo que implica altas tasas de morbimortalidad. El conocimiento de la epidemiología de estas infecciones nosocomiales asociadas con hongos es indispensable para instaurar una terapia antifúngica adecuada. Objetivos. Describir la epidemiologia de las infecciones causadas por Candida en las unidades de cuidados intensivos (UCI) de una red de vigilancia de Colombia. Métodos. La información se recogió en los laboratorios de microbiología de 20 instituciones de tercer nivel en 10 ciudades de Colombia a través de Whonet® versión 5.6. Se realizó un análisis descriptivo general de las especies de Candida más frecuentes y de su perfil de sensibilidad al fluconazol y al voriconazol desde 2010 hasta 2013, incluyendo un subanálisis de las infecciones asociadas con la atención de salud (IAAS) durante el último año. Resultados. De los 2.680 aislamientos de hongos, el 94,5% correspondió a especies de Candida, con proporciones similares entre Candida albicans y el resto de especies del género halladas (el 48,3 y el 51,7%, respectivamente). La mayor prevalencia entre estas últimas correspondió a Candida tropicalis (38,6%) y Candida parapsilosis (28,5%). En muestras de sangre, C. albicans no fue la especie más frecuente. La mayoría de especies fue sensible al fluconazol y al voriconazol. Candida causó el 25,5% de las IAAS reportadas, con la infección del torrente circulatorio asociada con catéter (58,8%) como la más frecuente de las patologías. No hubo diferencias estadísticamente significativas en el tiempo de estancia hospitalaria o en el de uso de cualquier eventual dispositivo entre las IAAS. Conclusiones. En las UCI de Colombia, la prevalencia de C. albicans es muy similar al del resto de especies en conjunto. Únicamente en sangre fue evidente el predominio de otras especies del género diferentes de C. albicans. Otros estudios son necesarios para evaluar factores asociados con la infección por Candida y determinar su impacto en estos pacientes (AU)

Epidemiology of Candida isolates from Intensive Care Units in Colombia from 2010 to 2013.

BACKGROUND: The frequency of Candida isolates as a cause of hospital infections has risen in recent years, leading to high rates of morbidity and mortality. The knowledge of the epidemiology of those hospital acquired fungal infections is essential to implement an adequate antifungal therapy. AIMS: To describe the epidemiology of Candida infections in Intensive Care Units (ICUs) from a surveillance network in Colombia. METHODS: Information was collected from the microbiology laboratories of 20 tertiary healthcare institutions from 10 Colombian cities using the Whonet® software version 5.6. A general descriptive analysis of Candida species and susceptibility profiles focusing on fluconazole and voriconazole was completed between 2010 and 2013, including a sub-analysis of healthcare associated infections (HAIs) during the last year. RESULTS: Candida isolates made up 94.5% of the 2680 fungal isolates considered, with similar proportions for Candida albicans and non-C. albicans Candida species (48.3% and 51.7%, respectively). Among the latter, Candida tropicalis (38.6%) and Candida parapsilosis (28.5%) were the most frequent species. Of note, among the blood isolates C. albicans was not the main species. Most of the species isolated were susceptible to fluconazole and voriconazole. From the HAIs reported, 25.5% were caused by Candida; central line-associated bloodstream infection was the most common HAI (58.8%). There were no statistically significant differences regarding length of hospital stay and device days among HAIs. CONCLUSIONS: In ICUs of Colombia, non-C. albicans Candida species are as frequent as C. albicans, except in blood samples where non-C. albicans Candida isolates predominate. Further studies are needed to evaluate Candida associated risk factors and to determine its clinical impact.

[Mortality risk factors associated with healthcare infections in a tertiary level university hospital in Colombia]. / Factores de riesgo asociados a mortalidad en infecciones relacionadas con la atención en salud en un hospital universitario de tercer nivel en Colombia.

INTRODUCTION: Nosocomial infections are a public health threat. Despite multiple efforts, its incidence is still significant and it generates high costs in health care. OBJECTIVE: To determine risk factors associated with mortality in patients with healthcare infections in a tertiary level hospital in Colombia. MATERIALS AND METHODS: A prospective cohort observational study was performed between January and December 2011. One thousand one hundred and fifteen patients with health care infections using the CDC definition criteria were included. Exclusion criteria were those patients with no microbiologic isolate associated with the infection or hospital readmissions in the last year. Socio-demographic and clinical variables, bacterial resistance profiles and antibiotic use were evaluated. Death was the primary outcome. Survival analysis for each variable was performed using statistical significance defined by the log-rank test. Multivariate and Cox regression analyses were done. Values of p less than 0.05 were considered statistically significant. RESULTS: Mean age was 43 years old (57% men and 47% women); 53% of patients had a medical condition and 47% surgical diagnosis; 54% of health care infections were surgical site infections and 62% were associated to Gram-negative bacilli. The mortality rate during follow-up was 24.4%. On multivariate analysis we found an association with intensive care stay (HR=1.51; 95% CI: 1.13-2.01), inappropriate use of antibiotics (HR=3.05; 95% CI: 2.34-3.98) and use of generic antibiotics or copies (HR=1.91; 95%CI: 1.43-2.55). CONCLUSIONS: The use of generic molecules of antibiotics and inappropriate antibiotic treatments in patients with health care infections are modifiable factors to decrease mortality.

Factores de riesgo asociados a mortalidad en infecciones relacionadas con la atención en salud en un hospital universitario de tercer nivel en Colombia / Mortality risk factors associated with healthcare infections in a tertiary level university hospital in Colombia

Introducción. Las infecciones hospitalarias son una amenaza para la salud pública. A pesar de los esfuerzos para contenerlas, su incidencia sigue siendo grande y genera altos costos en la atención en salud. Objetivo. Determinar los factores asociados a mortalidad en pacientes con diagnóstico de infecciones hospitalarias en nuestra institución. Materiales y métodos. Se llevó a cabo un estudio prospectivo de cohortes entre enero y diciembre del 2011 por medio de la observación de 1.015 pacientes con diagnóstico de infección de acuerdo a los criterios del sistema de vigilancia hospitalaria sugeridos por los Centers for Disease Control and Prevention (CDC). Se excluyó a quienes no tenían cultivo microbiológico de la infección o habían tenido reingresos hospitalarios en menos de un año. Se evaluaron variables sociodemográficas y clínicas, perfiles de resistencia microbiológica y uso de antibióticos. La variable de desenlace fue la muerte. Se realizó un análisis de supervivencia para cada variable, estableciendo significación estadística con la prueba de log-rank , así como un análisis multivariado mediante regresión de Cox. Se consideraron significativos los valores de p menores de 0,05. Resultados. El promedio de edad fue de 43 años (57 % hombres y 43 % mujeres); 53 % de los pacientes tuvo diagnóstico clínico y 47 %, quirúrgico; 54 % de las infecciones se presentó en la herida quirúrgica y 62 % de ellas se asociaron a microorganismos Gram negativos. La mortalidad durante el seguimiento fue de 24,4 %. En el análisis multivariado se encontró asociación con mortalidad para las variables de estancia en cuidado intensivo ( hazard ratio (HR)=1,51; IC 95% 1,13-2,01), uso inapropiado de antibióticos (HR=3,05; IC 95% 2,34-3,98) y uso de antibiótico genérico o copia (HR=1,91; IC IC 95% 1,43-2,55). Conclusiones. El empleo de moléculas genéricas y el uso inadecuado de antibióticos en pacientes con infecciones hospitalarias son factores que pueden modificarse para disminuir la mortalidad.

Introduction: Nosocomial infections are a public health threat. Despite multiple efforts, its incidence is still significant and it generates high costs in health care. Objective: To determine risk factors associated with mortality in patients with healthcare infections in a tertiary level hospital in Colombia. Materials and methods: A prospective cohort observational study was performed between January and December 2011. One thousand one hundred and fifteen patients with health care infections using the CDC definition criteria were included. Exclusion criteria were those patients with no microbiologic isolate associated with the infection or hospital readmissions in the last year. Socio-demographic and clinical variables, bacterial resistance profiles and antibiotic use were evaluated. Death was the primary outcome. Survival analysis for each variable was performed using statistical significance defined by the log-rank test. Multivariate and Cox regression analyses were done. Values of p less than 0.05 were considered statistically significant. Results: Mean age was 43 years old (57% men and 47% women); 53% of patients had a medical condition and 47% surgical diagnosis; 54% of health care infections were surgical site infections and 62% were associated to Gram-negative bacilli. The mortality rate during follow-up was 24.4%. On multivariate analysis we found an association with intensive care stay (HR=1.51; 95% CI: 1.13-2.01), inappropriate use of antibiotics (HR=3.05; 95% CI: 2.34-3.98) and use of generic antibiotics or copies (HR=1.91; 95%CI: 1.43-2.55). Conclusions: The use of generic molecules of antibiotics and inappropriate antibiotic treatments in patients with health care infections are modifiable factors to decrease mortality.

Implementación de un programa de uso regulado de antibióticos en 2 unidades de cuidado intensivo medico-quirúrgico en un hospital universitario de tercer nivel en Colombia / Implementation of a regulated antibiotic use program in two medical-surgical intensive units care in a third level mayor teaching hospital in Colombia

Objetivo: Evaluar el impacto de un programa de uso regulado de antibióticos en adherencia, consumo antibiótico y resistencia bacteriana en 2 unidades de cuidados intensivos (UCI) de un hospital universitario de tercer nivel en Colombia. Materiales y Método: Estudio prospectivo observacional de intervención que analiza 2 períodos en el tiempo en 2 UCI: preintervención (agosto de 2008 a febrero de 2009) y posintervención (marzo a septiembre de 2009). El estudio se llevó a cabo en el Hospital Universitario del Valle Evaristo García E.S.E. Se evaluaron: adherencia a guías de uso de antibióticos creadas por epidemiología hospitalaria, consumo antibiótico en dosis diaria definida e incidencia acumulada mensual de infección por Escherichia coli (E. coli) y Klebsiella pneumoniae (K. pneumoniae) BLEE, Pseudomonas aeruginosa (P. aeruginosa) resistente a quinolonas y cefalosporinas de cuarta generación, Staphylococcus aureus resistente a oxacilina y Acinetobacter baumannii multirresistente. Resultados: Se encontró adherencia a guías de uso de antibióticos superior al 80% para ambas UCI durante la intervención. Se redujo significativamente el consumo de meropenem (UCI-1 p = 0,009/UCI-2 p = 0,000), vancomicina (UCI-1 y UCI-2 p = 0,018), ceftriaxona (UCI-1 p = 0,015/ UCI-2 p = 0,018), ciprofloxacina (UCI-1 p = 0,027/UCI-2 p = 0,018), se incrementó el consumo de piperacilina/tazobactam (UCI-1 p = no significativa/UCI-2 p = 0,017) y cefepime (UCI-1 p = 0,028/UCI-2 p = 0,004). Se redujo la incidencia de infección por E. coli y K. pneumoniae BLEE + (UCI-1 83%/UCI-2 78%), P. aeruginosa resistente a ciprofloxacina (UCI-1 87%/UCI-2 82%) y cefalosporinas de cuarta generación (UCI-1 83%/UCI-2 76%). Conclusiones: La creación de un programa de uso regulado de antibióticos reduce significativamente el consumo y los costos de antibióticos en las UCI del Hospital Universitario del Valle y la infección por microorganismos resistentes.

Objective: To determine the impact of a Program of Regulated Use of Antibiotics in adherence, antibiotic use and bacterial resistance in two medical-surgical Intensive Units Care (ICU´s) in a third level mayor teaching hospital in Colombia. Materials and Methods: Prospective observational study of intervention that examines two time periods in two ICU: pre-intervention (august/2008 to February/2009) and post-intervention (march to September/2009). The study was carried out in the Hospital Universitario del Valle Evaristo García E.S.E. (H.U.V). We evaluated adherence to the antibiotic therapy guidelines established by Hospital Epidemiology, antibiotic use measured by Defined Daily Doses and monthly incidence of infection by ESBL producer E.coli and K.pneumoniae, P.aeruginosa fluoroquinolone and four generation cephalosporin resistant, oxacilin resistant S.aureus and multidrug resistant A.baumannii. Results: The adherence to the antibiotic guidelines of antibiotic use was greater to 80% for the both ICU during the intervention period. Antibiotic use was significantly reduced for meropenem (ICU1 p=0,009/ICU2 p=0,000), vancomycin (ICU1-ICU2 p=0,018), ceftriaxone (ICU1 p=0,015/ICU2 p=0,018), ciprofloxacin (ICU1 p=0,027/ICU2 p=0,018), and increased the used of piperacilin/tazobactam (ICU2 p=0,017), and cefepime (ICU1 p=0,028/ICU2 p=0,004). The incidences of infection by ESBL producer E.coli and K.pneumoniae (ICU1 83%/ ICU2 78%), ciprofloxacin resistant and four generation cephalosporin resistant P.aeruginosa (ICU1 87%/ ICU2 82%) and (ICU1 83%/ICU2 76%) ware also reduced. Conclusions: The implementation of a Program of Regulated Use of Antibiotics reduces antibiotics use and resistant micro-organism specific infection rate in the Hospital Universitario del Valle´s ICU.