Impact of antimicrobial stewardship programs on antibiotic consumption and antimicrobial resistance in four Colombian healthcare institutions.

BACKGROUND: Antimicrobial stewardship programs (ASPs) have become a fundamental pillar in optimizing antimicrobial usage, improving patient care, and reducing antimicrobial resistance (AMR). Herein we evaluated the impact of an ASP on antimicrobial consumption and AMR in Colombia. METHODS: We designed a retrospective observational study and measured trends in antibiotic consumption and AMR before and after the implementation of an ASP using interrupted time series analysis over a 4-year period (24 months before and 24 months after ASP implementation). RESULTS: ASPs were implemented according to the available resources in each of the institutions. Before ASP implementation, there was a trend toward an increase in the antibiotic consumption of all measured antimicrobials selected. Afterward, an overall decrease in antibiotic consumption was observed. The use of ertapenem and meropenem decreased in hospital wards, while a decrease in the use of ceftriaxone, cefepime, piperacillin/tazobactam, meropenem, and vancomycin was observed in intensive care units. After ASP implementation, the trend toward an increase of oxacillin-resistant Staphylococcus aureus, ceftriaxone-resistant Escherichia coli, and meropenem-resistant Pseudomonas aeruginosa was reversed. CONCLUSIONS: In our study, we showed that ASPs are a key strategy in tackling the emerging threat of AMR and have a positive impact on antibiotic consumption and resistance.

Comparative In Vitro Activity of Ceftolozane/Tazobactam against Clinical Isolates of Pseudomonas aeruginosa and Enterobacterales from Five Latin American Countries.

BACKGROUND: Ceftolozane/tazobactam (C/T) is a combination of an antipseudomonal oxyiminoaminothiazolyl cephalosporin with potent in vitro activity against Pseudomonas aeruginosa and tazobactam, a known ß-lactamase inhibitor. The aim of this study was to evaluate the activity of C/T against clinical isolates of P. aeruginosa and Enterobacterales collected from five Latin American countries between 2016 and 2017, before its clinical use in Latin America, and to compare it with the activity of other available broad-spectrum antimicrobial agents. METHODS: a total of 2760 clinical isolates (508 P. aeruginosa and 2252 Enterobacterales) were consecutively collected from 20 hospitals and susceptibility to C/T and comparator agents was tested and interpreted following the current guidelines. RESULTS: according to the CLSI breakpoints, 68.1% (346/508) of P. aeruginosa and 83.9% (1889/2252) of Enterobacterales isolates were susceptible to C/T. Overall, C/T demonstrated higher in vitro activity than currently available cephalosporins, piperacillin/tazobactam and carbapenems when tested against P. aeruginosa, and its performance in vitro was comparable to fosfomycin. When tested against Enterobacterales, it showed higher activity than cephalosporins and piperacillin/tazobactam, and similar activity to ertapenem. CONCLUSIONS: these results show that C/T is an active ß-lactam agent against clinical isolates of P. aeruginosa and Enterobacterales.

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.

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.

Detection of carbapenemase-producing Pseudomonas aeruginosa: Evaluation of the carbapenem inactivation method (CIM).

INTRODUCTION: The carbapenem inactivation method (CIM) is a cost-effective assay for detecting carbapenemases. However, its interpretation is unclear for Pseudomonas spp. We evaluate its accuracy when meropenem is changed to imipenem. METHODS: We analyzed 266 P. aeruginosa isolates. The CIM method consists of: resuspend bacterial colonies (a full 10µL loop) in 400µL water, in which a 10µg disk of meropenem/imipenem is immersed. After 2h of incubation (35°C), remove the disk, place it onto a Mueller-Hinton agar plate previously inoculated with Escherichia coli (ATCC 25922), and incubate at 35 ̊C between 18-24 h. Interpretation criteria (mm of inhibition zone): ≤19mm, positive; ≥25mm negative; 20-24mm, undetermined. RESULTS: Imipenem improves the sensitivity and specificity of CIM when compared to meropenem (99.4% and 98.9%, vs. 91.9% and 94.7%, respectively). CONCLUSIONS: The accuracy of CIM for carbapenemase detection in P. aeruginosa is increased with the use of imipenem.

Clinical and economic impact of generic versus brand name meropenem use in an intensive care unit in Colombia.

BACKGROUND: Recent studies suggest that sustained use of generic antibiotics may be associated with clinical failure and emergence of antibacterial resistance. The present study was designed to determine the clinical outcome between the use of generic meropenem (GM) and brand-name meropenem (BNM). Additionally, this study evaluated the economic impact of GM and BNM to determine if the former represents a cost-effective alternative to the latter. METHODS: Patients treated between January 2011 and May 2014 received GM while patients treated between June 2014 and March 2017 received BNM. Mortality was compared between groups. Total infection cost was defined by the cost of antimicrobial consumption, length of stay, and laboratory and imaging exams until infection resolution. FINDINGS: A total of 168 patients were included; survival rate for the 68 patients treated with GM was 38% compared to 59% in the patients treated with BNM. Multivariate analysis showed that the variables most strongly-associated with mortality were cardiovascular disease (OR 18.18, 95% CI 1.25-262.3, p = 0.033) and treatment with generic meropenem (OR 18.45, 95% CI 1.45-232.32, p = 0.024). On the other hand, total infection cost did not show a significant difference between groups (BNM $10,771 vs. GM $11,343; p = 0.91). INTERPRETATION: The present study suggests that patients treated with GM have a risk of death 18 times higher compared to those treated with BNM. Furthermore, economic analysis shows that GM is not more cost effective than BNM. SUMMARY: More studies measuring clinical outcomes are needed to confirm the clinical equivalence of brand-name versus generic antibiotics, not only for meropenem but also for other molecules.

[Clinical impact of ertapenem de-escalation in critically-ill patients with Enterobacteriaceae infections]. / Impacto clínico del desescalamiento a ertapenem en pacientes críticos con infecciones por Enterobacteriaceae.

BACKGROUND: Ertapenem has proven to be effective for extended-spectrum beta-lactamases-producing Enterobacteriaceae but lacks activity against non-fermenters; de-escalation to this antibiotic may reduce the selection of resistance to Pseudomonas aeruginosa and improve clinical outcomes. AIM: To evaluate the clinical impact of de-escalation from broad-spectrum anti-pseudomonal agents to ertapenem, a non-pseudomonal antibiotics for Enterobacteriaceae infections in critically-ill patients. METHODS: We conducted a prospective cohort study in adult patients admitted to intensive care units (ICUs) who had Enterobacteriaceae infections and were de-escalated from empiric anti-pseudomonal coverage to non-pseudomonal antibiotics. Cox proportional hazards models were performed comparing all-cause mortality and length of hospital stay between patients who remained on anti-pseudomonal coverage versus those who were de-escalated to ertapenem. RESULTS: 105 patients in the anti-pseudomonal group were compared to 148 patients in the ertapenem de-escalation group. De-escalation was associated with lower all-cause mortality compared to patients who remained on anti-pseudomonal coverage (adjusted Hazard Ratio 0.24; 95% CI: 0.12-0.46). The length of ICU stay was similar between the groups. DISCUSSION: ICU patients with Enterobacteriaceae infections de-escalated to ertapenem therapy had better outcomes compared to patients who remained on broad-spectrum, anti-pseudomonal therapy, suggesting that de-escalation is a safe approach amongst ICU patients.

[Antimicrobial Stewardship programs in Peru: A fundamental agreement]. / Programas de optimización del uso de antimicrobianos en Perú: Un acuerdo sobre lo fundamental.

BACKGROUND: Antimicrobial resistance (AMR) is a global threat to public health. Antibiotic stewardship programs (AMSP) promote the proper use of antimicrobials, improve clinical and economic outcomes, and helps containing the AMR. AIM: To evaluate the diagnostic phase of the AMS programs and early implementation of AMS at three high complexity hospitals that belong to the social security system in Peru. METHODS: A quasi-experimental multicenter study was implemented. The construction of the AMSP, microbiological baselines, antimicrobial consumption and consensus on AMS activities were evaluated at the diagnosis and early implementation periods of the AMSP. RESULTS: Following implementation, hospitals doubled their score of resources and processes available for the AMS program from 6.75 to 13.75. The prevalence of extended spectrum beta-lactamase producing enterobacteria was 50-60% while Pseudomonas aeruginosa averaged 69% resistance to carbapenems. The defined daily dose (DDD) of ceftriaxone was 13.63, vancomycin 7.35 and meropenem 6.73 in average. Hospitals A and C decreased the use of antimicrobials (30-50%). DISCUSSION: The implementation of the AMSP in the three hospitals was achieved through diverse strategies designed by multidisciplinary teams, which in addition to its articulation, reduce the consumption of broad spectrum antimicrobials at an early stage.

Distinct Genetic Diversity of Carbapenem-Resistant Acinetobacter baumannii from Colombian Hospitals.

The global success of multidrug-resistant Acinetobacter baumannii has been associated with the dissemination of a high-risk clone designated clonal complex (CC) 92B (Bartual scheme)/CC2P (Pasteur scheme), which is the most frequent genetic lineage in European, Asian, and North American carbapenem-resistant Acinetobacter isolates. In these isolates, carbapenem resistance is mainly mediated by ß-lactamases encoded by blaOXA-23-like, blaOXA-24-like, blaOXA-51-like, and/or blaOXA-58-like genes. In this study, we characterized the population genetics of 121 carbapenem-resistant A. baumannii complex isolates recovered from 14 hospitals in seven cities in Colombia (2008-2010). Multiplex PCR was used to detect blaOXA-23-like, blaOXA-24-like, blaOXA-51-like, and blaOXA-58-like genes. Molecular typing was performed using pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST). PCR showed that 118 (97.5%) of the isolates were positive for both blaOXA-23-like and blaOXA-51-like genes, and three other isolates were only positive for blaOXA-51-like. PFGE identified 18 different pulsotypes, while MLST identified 11 different sequence types (STs), seven of which had not been previously described in Acinetobacter. None of the STs found in this study was associated with CC92B/CC2P. The most widespread STs in our isolates belonged to ST636 and their single-locus variants ST121/ST124/ST634 (CC636B) followed by STs belonging to CC110B. Our observations suggest a wide distribution of diverse A. baumannii complex clones containing blaOXA-23-like in Colombian hospitals (especially CC636B and CC110B) that differ from the high-risk clones commonly found in other regions of the world, indicating a distinct molecular epidemiology of carbapenem-resistant Acinetobacter spp. in Colombia.

Molecular characterisation of carbapenem-resistant Enterobacter cloacae complex in Colombia: blaKPC and the 'changing landscape'.

OBJECTIVES: The aim of this study was to examine the population structure of representative carbapenem-resistant Enterobacter cloacae complex (CR-Ecl) isolates from eight different Colombian regions and to characterise their associated ß-lactamases. METHODS: A total of 28 CR-Ecl isolates collected in Colombia between 2009-2013 through the Colombian Nosocomial Network were included in this study. Antimicrobial susceptibility testing was performed by the broth microdilution method. Molecular detection of carbapenemase and extended-spectrum ß-lactamase (ESBL) genes and the presence of transposon Tn4401 was evaluated by PCR and DNA sequencing. Genetic relatedness was assessed by multilocus sequencing typing (MLST) and repetitive sequence-based PCR (rep-PCR). RESULTS: PCR and DNA sequencing revealed that 19/28 (68%) of the CR-Ecl isolates carried blaKPC-2. Analysis of the genetic environment found blaKPC-2 within transposon Tn4401b in 8/19 isolates (42%). Population genetic analysis using rep-PCR revealed four clonal groups. MLST showed a variety of sequence types (STs), among which ST510 was the most common (10/28 isolates; 36%). CONCLUSIONS: blaKPC-2 was discovered as the most common mechanism of carbapenem resistance in CR-Ecl and was disseminated among different STs. Although none of the previously reported major clonal complexes were identified, it appears that local strain lineages are associated with the spread of blaKPC within CR-Ecl in various regions of Colombia.

Characterization and Clinical Impact of Bloodstream Infection Caused by Carbapenemase-Producing Enterobacteriaceae in Seven Latin American Countries.

INTRODUCTION: Infections caused by carbapenem-resistant Enterobacteriaceae are a public health problem associated with higher mortality rates, longer hospitalization and increased healthcare costs. We carried out a study to describe the characteristics of patients with carbapenemase-producing Enterobacteriaceae (CPE) and non-CPE bloodstream infection (BSI) from Latin American hospitals and to determine the clinical impact in terms of mortality and antibiotic therapy. METHODS: Between July 2013 and November 2014, we conducted a multicenter observational study in 11 hospitals from 7 Latin American countries (Argentina, Colombia, Ecuador, Guatemala, Mexico, Peru, Venezuela). Patients with BSI caused by Enterobacteriaceae were included and classified either as CPE or non-CPE based on detection of blaKPC, blaVIM, blaIMP, blaNDM and blaOXA-48 by polymerase chain reaction. Enrolled subjects were followed until discharge or death. Demographic, microbiological and clinical characteristics were collected from medical records. Both descriptive and inferential statistics were used to analyze the information. RESULTS: A total of 255 patients with Enterobacteriaceae BSI were included; CPE were identified in 53 of them. In vitro non-susceptibility to all screened antibiotics was higher in the patients with CPE BSI, remaining colistin, tigecycline and amikacin as the most active drugs. Combination therapy was significantly more frequent in the CPE BSI group (p < 0.001). The most common regimen was carbapenem + colistin or polymyxin B. The overall mortality was 37% (94/255). Overall and attributable mortality were significantly higher in patients with CPE BSI (p < 0.001); however, we found that patients with CPE BSI who received combination therapy and those who received monotherapy had similar mortality. After multivariate adjustment, CPE BSI (adjusted odds ratio [aOR] 4; 95% confidence interval [CI] 1.7-9.5; p = 0.002) and critical illness (aOR 6.5; 95% CI 3.1-13.7; p < 0.001) were independently associated with in-hospital mortality. CONCLUSIONS: This study provides valuable data on the clinical characteristics and mortality risk factors in patients with CPE BSI. We determined that CPE infection is an independent mortality predictor and thus Latin American hospitals should perform campaigns on prevention and control of CPE BSI.

Introduction of software tools for epidemiological surveillance in infection control in Colombia.

INTRODUCTION: Healthcare-Associated Infections (HAI) are a challenge for patient safety in the hospitals. Infection control committees (ICC) should follow CDC definitions when monitoring HAI. The handmade method of epidemiological surveillance (ES) may affect the sensitivity and specificity of the monitoring system, while electronic surveillance can improve the performance, quality and traceability of recorded information. OBJECTIVE: To assess the implementation of a strategy for electronic surveillance of HAI, Bacterial Resistance and Antimicrobial Consumption by the ICC of 23 high-complexity clinics and hospitals in Colombia, during the period 2012-2013. METHODS: An observational study evaluating the introduction of electronic tools in the ICC was performed; we evaluated the structure and operation of the ICC, the degree of incorporation of the software HAI Solutions and the adherence to record the required information. RESULTS: Thirty-eight percent of hospitals (8/23) had active surveillance strategies with standard criteria of the CDC, and 87% of institutions adhered to the module of identification of cases using the HAI Solutions software. In contrast, compliance with the diligence of the risk factors for device-associated HAIs was 33%. CONCLUSIONS: The introduction of ES could achieve greater adherence to a model of active surveillance, standardized and prospective, helping to improve the validity and quality of the recorded information.

INTRODUCCIÓN: Las infecciones asociadas a la atención en salud (IAAS) son un reto para la seguridad del paciente. Los comités de infecciones hospitalarios (CIH) deben realizar una vigilancia epidemiológica (VE) de las IAAS siguiendo los criterios de los Centros para el Control y Prevención de Enfermedades - EE.UU (CDC). La VE manual afecta la sensibilidad y especificidad del sistema de vigilancia, mientras que la VE electrónica mejora el desempeño, calidad y trazabilidad de la información registrada. OBJETIVO: Evaluar la implementación de una estrategia para la VE electrónica de las IAAS, resistencia bacteriana, consumo de antimicrobianos y características de los CIH en 23 clínicas y hospitales de alta complejidad en Colombia, en el periodo 2012-2013. MÉTODOS: Se realizó un estudio observacional descriptivo de la introducción de herramientas informáticas en los CIH, evaluando la estructura y funcionamiento de los CIH, el grado de incorporación del software HAI Solutions y la cumplimiento al registro de la información requerida. RESULTADOS: El 38% de las clínicas y hospitales (8/23) presentaron estrategias de vigilancia epidemiológica activa con criterios estándar del CDC. El 87% de las instituciones se adhirieron al módulo de captación de casos del software HAI Solutions, y el cumplimiento del diligenciamiento de los factores de riesgo de las IAAS asociadas a dispositivos fue del 33%. CONCLUSIONES: La introducción del modelo de VE electrónica podría lograr un mayor cumplimiento a un modelo de vigilancia epidemiológica activo, estandarizado y prospectivo, contribuyendo al mejoramiento en la validez y calidad de la información registrada.

[Evolution of antimicrobial resistance in Gram negative bacilli from intensive care units in Colombia]. / Evolución de la resistencia antimicrobiana de bacilos Gram negativos en unidades de cuidados intensivos en Colombia.

INTRODUCTION: The continuous evolution of antimicrobial resistance poses a major threat to public health worldwide. Molecular biology techniques have been integrated to epidemiological surveillance systems to improve the control strategies of this phenomenon. OBJECTIVE: To describe the phenotypic and molecular profiles of the most important Gram negative bacilli from intensive care units in 23 Colombian hospitals during the study period 2009-2012. MATERIALS AND METHODS: A descriptive study was conducted in 23 hospitals belonging to the Colombian Nosocomial Resistance Study Group. A total of 38.048 bacterial isolates were analyzed using WHONET over a four-year period. The antimicrobial resistant profiles were described for Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Acinetobacter baumannii . Polymerase chain reaction was performed in 1.248 strains to detect the most clinically relevant carbapenemases. RESULTS: Escherichia coli was the most frequently isolated organism (mean=14.8%). Frequency of K. pneumoniae increased significantly from 11% in 2009 to 15% in 2012 (p<0.001). All screened isolates had rising trends of multidrug-resistant profiles. KPC ( Klebsiella pneumoniae carbapenemase) was detected in 68.4% of K. pneumoniae isolates while VIM (Verona integron-encoded metallo-betalactamase) was present in 46.5% of them. CONCLUSION: In this study, an increase in the trend of multidrug-resistant organisms and a wide distribution of carbapenemases was observed. The integration of molecular biology to surveillance systems allowed the compilation of this data, which will aid in the construction of guidelines on antimicrobial stewardship for prevention in Colombia.

Detection of carbapenemase-producing Pseudomonas aeruginosa: Evaluation of the carbapenem inactivation method (CIM) / Detección de Pseudomonas aeruginosa productoras de carbapenemasas: evaluación del método de inactivación de carbapenem

INTRODUCTION: The carbapenem inactivation method (CIM) is a cost-effective assay for detecting carbapenemases. However, its interpretation is unclear for Pseudomonas spp. We evaluate its accuracy when meropenem is changed to imipenem. METHODS: We analyzed 266 P. aeruginosa isolates. The CIM method consists of: resuspend bacterial colonies (a full 10 μ,L loop) in 400 μ,L water, in which a 10 μ,g disk of meropenem/imipenem is immersed. After 2 h of incubation (35°C), remove the disk, place it onto a Mueller-Hinton agar plate previously inoculated with Escherichia coli (ATCC 25922), and incubate at 35 ̊C between 18-24 h. Interpretation criteria (mm of inhibition zone): ≤ 19 mm, positive; ≥ 25 mm negative; 20-24 mm, undetermined. RESULTS: Imipenem improves the sensitivity and specificity of CIM when compared to meropenem (99.4% and 98.9%, vs. 91.9% and 94.7%, respectively). CONCLUSIONS: The accuracy of CIM for carbapenemase detection in P. aeruginosa is increased with the use of imipenem

INTRODUCCIÓN: El método de inactivación del carbapenem (CIM, por sus siglas en inglés) se utiliza para detectar carbapenemasas, pero su interpretación no está clara para Pseudomonas spp. Se evaluó la precisión del método utilizando imipenem en lugar de meropenem. MÉTODOS: Se estudiaron 266 aislados de P. aeruginosa. El CIM consiste en: suspender colonias bacterianas (un asa de 10 μ,l) en 400 μ,l de agua en los que se sumerge un disco de 10 μ,g de meropenem/imipenem. Tras 2 h de incubación (35°C) se saca el disco y es transferido a agar Mueller-Hinton, previamente inoculado con Escherichia coli (ATCC 25922) e incubado a 35°C entre 18-24h. Criterios de interpretación (mm halo de inhibición): ≤ 19 mm positivo; ≥ 25 mm negativo y 20-24 mm indeterminado. RESULTADOS: Imipenem mejora la sensibilidad y especificidad del CIM frente a meropenem (99,4 y 98,9% vs. 91,9 y 94,7%, respectivamente). CONCLUSIONES: La precisión del CIM para la detección de carbapenemasas en P. aeruginosa mejora al utilizar imipenem

Clinical and economic impact of generic versus brand name meropenem use in an intensive care unit in Colombia

Abstract Background: Recent studies suggest that sustained use of generic antibiotics may be associated with clinical failure and emergence of antibacterial resistance. The present study was designed to determine the clinical outcome between the use of generic meropenem (GM) and brand-name meropenem (BNM). Additionally, this study evaluated the economic impact of GM and BNM to determine if the former represents a cost-effective alternative to the latter. Methods: Patients treated between January 2011 and May 2014 received GM while patients treated between June 2014 and March 2017 received BNM. Mortality was compared between groups. Total infection cost was defined by the cost of antimicrobial consumption, length of stay, and laboratory and imaging exams until infection resolution. Findings: A total of 168 patients were included; survival rate for the 68 patients treated with GM was 38% compared to 59% in the patients treated with BNM. Multivariate analysis showed that the variables most strongly-associated with mortality were cardiovascular disease (OR 18.18, 95% CI 1.25-262.3, p = 0.033) and treatment with generic meropenem (OR 18.45, 95% CI 1.45-232.32, p = 0.024). On the other hand, total infection cost did not show a significant difference between groups (BNM $10,771 vs. GM $11,343; p = 0.91). Interpretation: The present study suggests that patients treated with GM have a risk of death 18 times higher compared to those treated with BNM. Furthermore, economic analysis shows that GM is not more cost effective than BNM. Summary: More studies measuring clinical outcomes are needed to confirm the clinical equivalence of brand-name versus generic antibiotics, not only for meropenem but also for other molecules.

Programas de optimización del uso de antimicrobianos en Perú: un acuerdo sobre lo fundamental / Antimicrobial Stewardship programs in Peru: a fundamental agreement

Resumen Introducción: La resistencia a los antimicrobianos (RAM) es una amenaza para la salud pública mundial. Los programas de optimización del uso de antimicrobianos (PROAs) son programas que promueven su adecuado uso, mejoran los resultados clínicos, económicos y contribuyen a contener la RAM. Objetivos: Evaluar las fases de diagnóstico e implementación temprana de los PROAs en tres hospitales de alta complejidad pertenecientes al Sistema de Seguridad Social del Perú. Materiales y Métodos: Estudio multicéntrico, cuasi experimental. La estructuración de los programas, las líneas de base microbiológicas, el consumo de antimicrobianos y los consensos fueron evaluadas durante los períodos de diagnóstico inicial y durante la implementación temprana de los PROAs. Resultados: Con posterioridad a la implementación, los hospitales duplicaron la puntuación de recursos disponibles para los programas (6,75 vs 13,75). La prevalencia de enterobacterias portadoras de β-lactamasas de espectro extendido era de 50-60%, mientras que la resistencia a carbapenémicos en Pseudomonas aeruginosa promedió el 69%. La dosis diaria definida de ceftriaxona fue de 13,63, de 7,35 para vancomicina y 6,73 para meropenem en promedio. Los hospitales A y C disminuyeron el uso de antimicrobianos en 30 a 50%. Discusión: A través de estrategias diseñadas por equipos multidisciplinarios para implementar los PROAs, se logró disminuir tempranamente el consumo de antimicrobianos de amplio espectro.

Background. Antimicrobial resistance (AMR) is a global threat to public health. Antibiotic stewardship programs (AMSP) promote the proper use of antimicrobials, improve clinical and economic outcomes, and helps containing the AMR. Aim: To evaluate the diagnostic phase of the AMS programs and early implementation of AMS at three high complexity hospitals that belong to the social security system in Peru. Methods: A quasi-experimental multicenter study was implemented. The construction of the AMSP, microbiological baselines, antimicrobial consumption and consensus on AMS activities were evaluated at the diagnosis and early implementation periods of the AMSP. Results: Following implementation, hospitals doubled their score of resources and processes available for the AMS program from 6.75 to 13.75. The prevalence of extended spectrum beta-lactamase producing enterobacteria was 50-60% while Pseudomonas aeruginosa averaged 69% resistance to carbapenems. The defined daily dose (DDD) of ceftriaxone was 13.63, vancomycin 7.35 and meropenem 6.73 in average. Hospitals A and C decreased the use of antimicrobials (30-50%). Discussion: The implementation of the AMSP in the three hospitals was achieved through diverse strategies designed by multidisciplinary teams, which in addition to its articulation, reduce the consumption of broad spectrum antimicrobials at an early stage.

Impacto clínico del desescalamiento a ertapenem en pacientes críticos con infecciones por Enterobacteriaceae / Clinical impact of ertapenem de-escalation in critically-ill patients with Enterobacteriaceae infections

Resumen Introducción: Ertapenem ha demostrado eficacia frente a Enterobacteriaceae productoras de β-lactamasas de espectro extendido, pero carece de actividad contra bacterias no fermentadoras; el desescalamiento a este antimicrobiano cuando no existe la presencia de P. aeruginosa podría reducir la presión selectiva contra esta bacteria y mejorar los resultados clínicos. Objetivo: Evaluar el impacto clínico del desescalamiento de antimicrobianos con cobertura anti-pseudomonas a ertapenem, un agente sin este espectro, en pacientes críticos con infecciones por Enterobacteriaceae. Métodos: Se realizó un estudio de cohorte prospectivo en adultos admitidos a Unidades de Cuidado Intensivo (UCI) con infecciones por Enterobacteriaceae, que habían sido desescalados de una cobertura anti-pseudomonas, a un antimicrobiano sin la misma (ertapenem). Se realizó un modelo de riesgo proporcional de Cox comparando mortalidad por cualquier causa y duración de estancia hospitalaria entre aquellos pacientes que permanecieron con cobertura anti-pseudomonas versus aquellos que fueron desescalados a ertapenem. Resultados: 105 pacientes en el grupo anti-pseudomonas fueron comparados con 148 pacientes del grupo de desescalamiento a ertapenem. El desescalamiento estuvo asociado con una menor mortalidad por cualquier causa comparado con los pacientes que permanecieron con cobertura anti-pseudomonas (hazard ratio ajustado 0,24; IC 95%: 0,12-0,46). La estancia hospitalaria en UCI fue similar en ambos grupos. Discusión: Los pacientes de UCI con infecciones por Enterobacteriaceae desescalados a terapia con ertapenem, tuvieron mejores resultados clínicos comparados con aquellos que permanecieron en terapia anti-pseudomonas, sugiriendo que el desescalamiento es una práctica segura en esta población.

Background: Ertapenem has proven to be effective for extended-spectrum beta-lactamases-producing Enterobacteriaceae but lacks activity against non-fermenters; de-escalation to this antibiotic may reduce the selection of resistance to Pseudomonas aeruginosa and improve clinical outcomes. Aim: To evaluate the clinical impact of de-escalation from broad-spectrum anti-pseudomonal agents to ertapenem, a non-pseudomonal antibiotics for Enterobacteriaceae infections in critically-ill patients. Methods: We conducted a prospective cohort study in adult patients admitted to intensive care units (ICUs) who had Enterobacteriaceae infections and were de-escalated from empiric anti-pseudomonal coverage to non-pseudomonal antibiotics. Cox proportional hazards models were performed comparing all-cause mortality and length of hospital stay between patients who remained on anti-pseudomonal coverage versus those who were de-escalated to ertapenem. Results: 105 patients in the anti-pseudomonal group were compared to 148 patients in the ertapenem de-escalation group. De-escalation was associated with lower all-cause mortality compared to patients who remained on anti-pseudomonal coverage (adjusted Hazard Ratio 0.24; 95% CI: 0.12-0.46). The length of ICU stay was similar between the groups. Discussion: ICU patients with Enterobacteriaceae infections de-escalated to ertapenem therapy had better outcomes compared to patients who remained on broad-spectrum, anti-pseudomonal therapy, suggesting that de-escalation is a safe approach amongst ICU patients.

Optimización de la antibioticoterapia, una estrategia en contra de la multirresistencia microbiana / Optimization of antibiotic therapy, a strategy against microbial multidrug resistance

Durante el último siglo, los agentes antimicrobianos transformaron la práctica de la medicina. De la mano de los antimicrobianos se han logrado grandes avances en el tratamiento de las enfermedades infecciosas, permitiendo, además, que el manejo exitoso de pacientes críticamente enfermos, en quimioterapia o con necesidad de trasplantes de órganos sea una realidad (1,2). Sin embargo, entre el 20 y el 50 % de las prescripciones de antimicrobianos en instituciones hospitalarias de cuidado crítico en Estados Unidos son innecesarias o inapropiadas (3). El uso inadecuado de los antimicrobianos es un factor definitivo para la generación y el incremento progresivo de la resistencia microbiana, la cual puede diseminarse por medio de elementos genéticos móviles a otras bacterias del ámbito hospitalario y de la comunidad; por esta razón, la resistencia bacteriana podría considerarse la mayor amenaza actual en salud pública (4). Los programas de optimización de la antibioticoterapia (antimicrobial stewardship) pretenden racionalizar el manejo de las alternativas terapéuticas en los pacientes con infecciones, incrementando las tasas de curación, disminuyendo la probabilidad de fallas y reduciendo los efectos secundarios asociados al uso de antimicrobianos (4).

Introduction of software tools for epidemiological surveillance in infection control in Colombia / Introducción de herramientas informáticas para la vigilancia epidemiológica en el control de infecciones en Colombia

Introduction: Healthcare-Associated Infections (HAI) are a challenge for patient safety in the hospitals. Infection control committees (ICC) should follow CDC definitions when monitoring HAI. The handmade method of epidemiological surveillance (ES) may affect the sensitivity and specificity of the monitoring system, while electronic surveillance can improve the performance, quality and traceability of recorded information. Objective: To assess the implementation of a strategy for electronic surveillance of HAI, Bacterial Resistance and Antimicrobial Consumption by the ICC of 23 high-complexity clinics and hospitals in Colombia, during the period 2012-2013. Methods: An observational study evaluating the introduction of electronic tools in the ICC was performed; we evaluated the structure and operation of the ICC, the degree of incorporation of the software HAI Solutions and the adherence to record the required information. Results: Thirty-eight percent of hospitals (8/23) had active surveillance strategies with standard criteria of the CDC, and 87% of institutions adhered to the module of identification of cases using the HAI Solutions software. In contrast, compliance with the diligence of the risk factors for device-associated HAIs was 33%.

Introducción: Las infecciones asociadas a la atención en salud (IAAS) son un reto para la seguridad del paciente. Los comités de infecciones hospitalarios (CIH) deben realizar una vigilancia epidemiológica (VE) de las IAAS siguiendo los criterios de los Centros para el Control y Prevención de Enfermedades - EE.UU (CDC). La VE manual afecta la sensibilidad y especificidad del sistema de vigilancia, mientras que la VE electrónica mejora el desempeño, calidad y trazabilidad de la información registrada. Objetivo: Evaluar la implementación de una estrategia para la VE electrónica de las IAAS, resistencia bacteriana, consumo de antimicrobianos y características de los CIH en 23 clínicas y hospitales de alta complejidad en Colombia, en el periodo 2012-2013. Métodos: Se realizó un estudio observacional descriptivo de la introducción de herramientas informáticas en los CIH, evaluando la estructura y funcionamiento de los CIH, el grado de incorporación del software HAI Solutions y la cumplimiento al registro de la información requerida. Resultados: El 38% de las clínicas y hospitales (8/23) presentaron estrategias de vigilancia epidemiológica activa con criterios estándar del CDC. El 87% de las instituciones se adhirieron al módulo de captación de casos del software HAI Solutions, y el cumplimiento del diligenciamiento de los factores de riesgo de las IAAS asociadas a dispositivos fue del 33%. Conclusiones: La introducción del modelo de VE electrónica podría lograr un mayor cumplimiento a un modelo de vigilancia epidemiológica activo, estandarizado y prospectivo, contribuyendo al mejoramiento en la validez y calidad de la información registrada.