Driving multisectoral antimicrobial resistance action in South America: Lessons learned from implementing an enhanced tripartite AMR country self-assessment tool.

As part of an innovative Tripartite-EU collaboration Project that supports seven South American countries, a Landscape Analysis Tool (LAT) was developed and implemented to collect data to complement the Tripartite AMR Country Self-Assessment Survey (TrACSS) process. The LAT enables collection of broader and deeper information to guide development of priority One Health activities, and strengthen national action plans to combat antimicrobial resistance. The Project developed the tool, trained a consultant pool in its use, and implemented it in conjunction with multi-sectoral country teams. The main results were seven priority-informed country workplans that proposed specific activities in line with the Strategic Objectives of each country's national action plan. LAT implementation clearly showed that the tool is a strong complement to the TrACSS process and that there can be considerable benefit to the process of collecting additional data layers, especially to strengthen country ownership of AMR-related information and solidifying multisectoral engagement. Countries elsewhere might consider implementing this complementary tool - either once to establish a baseline - or periodically to gain a better ongoing understanding of the situation on the ground.

[Evolution of the performance of Latin America Reference Laboratories in the detection of mechanisms of antimicrobial resistanceEvolução do desempenho dos Laboratórios de Referência na América Latina na detecção de mecanismos de resistência antimicrobiana]. / Evolución del desempeño de Laboratorios de Referencia de América Latina en la detección de mecanismos de resistencia a los antimicrobianos.

OBJECTIVE: The objective is to present the results of the Latin American Program for Quality Assurance in Bacteriology and Antimicrobial Resistance (LA-EQAS) between 2000 and 2018 and the evolution of the detection of resistance mechanisms with clinical impact. METHODS: The participating National Reference Laboratories (NRLs) received 25 surveys with 10 strains in each one, representing a total of 86 bacterial species and 40 resistance mechanisms. To evaluate the performance of the NRLs, five indicators were analyzed: bacterial identification, interpretation of susceptibility testing, acceptable ranges for zones of inhibition, inferred resistance mechanism, and delay time for the response. RESULTS: The average concordance was 82.6% (range: 74-95%) for bacterial identification, 93.3% (85-98%) for the interpretation of susceptibility testing, 84.6% (70-94%) for the zones of inhibition, and 82.5% (73-96%) for the inferred resistance mechanisms. The average delay time for the response was 34 days. Improvements in the detection of mechanisms of clinical importance, such as resistance to methicillin, macrolides and glycopeptides in Gram-positive cocci, and extended-spectrum, AmpC plasmid and carbapenemase beta-lactamases in Gram-negative bacilli, were observed. CONCLUSIONS: The LA-EQAS is an excellent tool for continuous quality improvement in the diagnosis of infections due to multiresistant microorganisms in NRLs in Latin America.

OBJETIVO: O objetivo deste trabalho é apresentar os resultados do Programa Latino-Americano de Garantia da Qualidade em Bacteriologia e Resistência Antimicrobiana (LA-EQAS, na sigla em inglês) entre 2000 e 2018 e a evolução na detecção de mecanismos de resistência com impacto clínico. MÉTODOS: Os Laboratórios Nacionais de Referência (LNRs) participantes receberam 25 inquéritos com 10 cepas bacterianas cada, representando um total de 86 espécies bacterianas e 40 mecanismos de resistência. Para avaliar o desempenho dos LNRs, foram analisados cinco indicadores: identificação bacteriana, interpretação dos testes de sensibilidade, faixas das zonas de inibição aceitáveis, mecanismo de resistência inferido e tempo de demora na resposta. RESULTADOS: A concordância média foi de 82,6% (intervalo: 74-95%) na identificação bacteriana, 93,3% (85-98%) na interpretação dos testes de sensibilidade, 84,6% (70-94%) nas zonas de inibição, 82,5% (73-96%) no mecanismo de resistência inferido e 34 dias na demora na resposta. Observou-se uma melhoria na detecção de mecanismos clinicamente relevantes, como a resistência a meticilina, macrolídeos e glicopeptídeos em cocos Gram-positivos, beta-lactamases de espectro ampliado, AmpC plasmídica e carbapenemases em bacilos Gram-negativos. CONCLUSÕES: O LA-EQAS é uma excelente ferramenta para a melhoria contínua da qualidade no diagnóstico de infecções por microrganismos multirresistentes nos LNRs da América Latina.

Evolución del desempeño de Laboratorios de Referencia de América Latina en la detección de mecanismos de resistencia a los antimicrobianos

[RESUMEN]. Objetivo. El objetivo es presentar los resultados del Programa Latinoamericano de Aseguramiento de la Calidad en Bacteriología y Resistencia a los Antimicrobianos (LA-EQAS) entre 2000 y 2018 y la evolución en la detección de mecanismos de resistencia de impacto clínico. Métodos. Los Laboratorios Nacionales de Referencia (LNR) participantes recibieron 25 encuestas con 10 cepas cada una, representando un total de 86 especies bacterianas y 40 mecanismos de resistencia. Para evaluar el desempeño de los LNR, se analizaron cinco indicadores: identificación bacteriana, interpretación de las pruebas de sensibilidad, rangos de las zonas de inhibición aceptables, mecanismo de resistencia inferido, y tiempo de demora en la respuesta. Resultados. La concordancia media fue 82,6% (rango: 74-95%) en la identificación bacteriana, 93,3% (85-98%) en la interpretación de las pruebas de sensibilidad, 84,6% (70-94%) en las zonas de inhibición, 82,5% (73-96%) en el mecanismo de resistencia inferido, y la demora en la respuesta, 34 días. Se observó una mejora en la detección de mecanismos de relevancia clínica como resistencia a meticilina, macrólidos y glucopéptidos en cocos gram positivos, y betalactamasas de espectro extendido, AmpC plasmídico y carbapenemasas en bacilos gram negativos. Conclusiones. El LA-EQAS es una excelente herramienta para la mejora continua de la calidad en el diagnóstico de las infecciones por microorganismos multirresistentes en los LNR de América Latina.

[RESUMEN]. Objetivo. El objetivo es presentar los resultados del Programa Latinoamericano de Aseguramiento de la Calidad en Bacteriología y Resistencia a los Antimicrobianos (LA-EQAS) entre 2000 y 2018 y la evolución en la detección de mecanismos de resistencia de impacto clínico. Métodos. Los Laboratorios Nacionales de Referencia (LNR) participantes recibieron 25 encuestas con 10 cepas cada una, representando un total de 86 especies bacterianas y 40 mecanismos de resistencia. Para evaluar el desempeño de los LNR, se analizaron cinco indicadores: identificación bacteriana, interpretación de las pruebas de sensibilidad, rangos de las zonas de inhibición aceptables, mecanismo de resistencia inferido, y tiempo de demora en la respuesta. Resultados. La concordancia media fue 82,6% (rango: 74-95%) en la identificación bacteriana, 93,3% (85-98%) en la interpretación de las pruebas de sensibilidad, 84,6% (70-94%) en las zonas de inhibición, 82,5% (73-96%) en el mecanismo de resistencia inferido, y la demora en la respuesta, 34 días. Se observó una mejora en la detección de mecanismos de relevancia clínica como resistencia a meticilina, macrólidos y glucopéptidos en cocos gram positivos, y betalactamasas de espectro extendido, AmpC plasmídico y carbapenemasas en bacilos gram negativos. Conclusiones. El LA-EQAS es una excelente herramienta para la mejora continua de la calidad en el diagnóstico de las infecciones por microorganismos multirresistentes en los LNR de América Latina.

[RESUMO]. Objetivo. O objetivo deste trabalho é apresentar os resultados do Programa Latino-Americano de Garantia da Qualidade em Bacteriologia e Resistência Antimicrobiana (LA-EQAS, na sigla em inglês) entre 2000 e 2018 e a evolução na detecção de mecanismos de resistência com impacto clínico. Métodos. Os Laboratórios Nacionais de Referência (LNRs) participantes receberam 25 inquéritos com 10 cepas bacterianas cada, representando um total de 86 espécies bacterianas e 40 mecanismos de resistência. Para avaliar o desempenho dos LNRs, foram analisados cinco indicadores: identificação bacteriana, interpretação dos testes de sensibilidade, faixas das zonas de inibição aceitáveis, mecanismo de resistência inferido e tempo de demora na resposta. Resultados. A concordância média foi de 82,6% (intervalo: 74-95%) na identificação bacteriana, 93,3% (85-98%) na interpretação dos testes de sensibilidade, 84,6% (70-94%) nas zonas de inibição, 82,5% (73-96%) no mecanismo de resistência inferido e 34 dias na demora na resposta. Observou-se uma melhoria na detecção de mecanismos clinicamente relevantes, como a resistência a meticilina, macrolídeos e glicopeptídeos em cocos Gram-positivos, beta-lactamases de espectro ampliado, AmpC plasmídica e carbapenemases em bacilos Gram-negativos. Conclusões. O LA-EQAS é uma excelente ferramenta para a melhoria contínua da qualidade no diagnóstico de infecções por microrganismos multirresistentes nos LNRs da América Latina.

Strong correlation between the rates of intrinsically antibiotic-resistant species and the rates of acquired resistance in Gram-negative species causing bacteraemia, EU/EEA, 2016.

BackgroundAntibiotic resistance, either intrinsic or acquired, is a major obstacle for treating bacterial infections.AimOur objective was to compare the country-specific species distribution of the four Gram-negative species Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa and Acinetobacter species and the proportions of selected acquired resistance traits within these species.MethodWe used data reported for 2016 to the European Antimicrobial Resistance Surveillance Network (EARS-Net) by 30 countries in the European Union and European Economic Area.ResultsThe country-specific species distribution varied considerably. While E. coli accounted for 31.9% to 81.0% (median: 69.0%) of all reported isolates, the two most common intrinsically resistant species P. aeruginosa and Acinetobacter spp. combined (PSEACI) accounted for 5.5% to 39.2% of isolates (median: 10.1%). Similarly, large national differences were noted for the percentages of acquired non-susceptibility to third-generation cephalosporins, carbapenems and fluoroquinolones. There was a strong positive rank correlation between the country-specific percentages of PSEACI and the percentages of non-susceptibility to the above antibiotics in all four species (rho > 0.75 for 10 of the 11 pairs of variables tested).ConclusionCountries with the highest proportion of P. aeruginosa and Acinetobacter spp. were also those where the rates of acquired non-susceptibility in all four studied species were highest. The differences are probably related to national differences in antibiotic consumption and infection prevention and control routines.

Characterizing Shigella species distribution and antimicrobial susceptibility to ciprofloxacin and nalidixic acid in Latin America between 2000-2015.

BACKGROUND: Shigellosis is the second leading cause of diarrheal death globally. The global burden has been complicated by the emergence of Shigella strains resistant to first line antibiotic treatments such as ciprofloxacin. This study aims to describe the epidemiologic distribution of the most common Shigella species, and their antimicrobial susceptibility patterns to ciprofloxacin and nalidixic acid (NA) in Latin America. METHODS: Laboratory data from 19 countries were obtained through the Latin American Network for Antimicrobial Resistance Surveillance (ReLAVRA) from 2000-2015. The Clinical Laboratory Standards Institute reduced susceptibility breakpoints for Enterobacteriaceae was used to interpret the disc diffusion tests for Shigella susceptibility to ciprofloxacin and NA. Negative binominal regression was used to analyze longitudinal trends of Shigella isolates antimicrobial susceptibility. RESULTS: 79,548 Shigella isolates were tested and reported between 2000-2015. The most common isolated species were S. flexneri (49%), and S. sonnei (28%). There was a steady increase in the proportion of S. sonnei isolates within the region(p<0.001). The average annual percentage increase (AAPI) in nonsusceptibility was 18.4% (p<0.001) for ciprofloxacin (baseline = 0.3); and 13.2%(p<0.001) for NA (baseline = 3). AAPI nonsusceptibility to ciprofloxacin was 13.3% for S. flexneri (p<0.04); and 39.9% for S. sonnei (p<0.001). Honduras, Dominican Republic, Venezuela, and Chile reported the highest increase in nonsusceptibility to ciprofloxacin among all Shigella isolates. CONCLUSION: There is an increasing trend in Shigella nonsusceptibility to ciprofloxacin and NA, including among the most common shigella species, in Latin America. This rise of nonsusceptibility among Shigella species to commonly used treatments such as ciprofloxacin is alarming and threatens the control and management of this currently treatable infection. Improved data quality, collection and reporting is needed in Latin America to respond effectively to the rising trends observed. This includes the need for quality isolate level epidemiological data; molecular data, and data on antibiotic consumption and use.

Heart failure following STEMI: a contemporary cohort study of incidence and prognostic factors.

Objective: The aim of the current study was to determine the contemporary incidence, risk factors and prognosis of heart failure (HF) after ST-elevation myocardial infarction (STEMI). Methods: We used the Arrhythmia Genetics in the Netherlands observational cohort study to identify patients with a first STEMI from 2001 onwards (n=1459). HF during follow-up was defined as hospitalisation for HF or an outpatient clinic visit for HF. Cox regression was performed to estimate the relationship between baseline covariates and the onset of HF. Results: Follow-up was completed for 1360 (93.2%) patients with an overall median follow-up time of 6.7 years, 1232 (90.6%) of these patients had undergone primary percutaneous coronary intervention (PCI). A total of 85 patients (6.3%) developed HF during follow-up. HF cases were significantly older at their index MI (59.9 vs 57.2 years, P<0.001) and more commonly had a history of atrial fibrillation (6.1% vs 1.4%, P=0.001) than controls without HF. The crude incidence rate of HF after STEMI was 9.7 (95% CI 7.7 to 11.8) per 1000 person-years. In multivariable analysis, peak creatine kinase MB (CK-MB) levels (HR 1.11 per 100 U/L (95% CI 1.11 to 1.22)) and a left anterior descending artery (LAD) culprit lesion (HR 2.88 (95% CI 1.53 to 5.40)) were risk factors associated with HF. Conclusions: We found a relatively low long-term contemporary incidence of HF after a first STEMI in the current PCI era in comparison with other reports. Higher CK-MB levels and a LAD culprit lesion at index STEMI were important risk factors for the development of HF after STEMI. Trial registration number: NCT03007199; Results.

Impact of livestock-associated MRSA in a hospital setting.

OBJECTIVES: The Netherlands is known for a stringent search and destroy policy to prevent spread of MRSA. In the hospital setting, livestock-associated MRSA (LA-MRSA) is frequently found in patients coming from the high density farming area in the south of the Netherlands. The aim of the study was to determine the contribution of LA-MRSA in the epidemiology of MRSA in cases found following the Dutch search and destroy policy. PATIENTS AND METHODS: From two hospitals serving a population of 550,000 persons all data on MRSA cultures and subsequent control measures from 2008 and 2009 were retrospectively collected and analyzed. RESULTS: A total of 3856 potential index patients were screened for MRSA, 373 (9.7%) were found to be positive, 292 ( 78%) LA-MRSA and 81 (22%) non-LA-MRSA respectively. No secondary cases were found among contact research in persons exposed to LA-MRSA (0/416), whereas similar contact research for non-LA-MRSA resulted in 83 (2.5%) secondary cases. LA-MRSA were rarely found to cause infections. CONCLUSIONS: LA-MRSA is more prevalent than non-LA-MRSA in Dutch Hospitals in the South of the Netherlands. However, retrospectively studied cases show that the transmission rate for LA-MRSA was much lower than for non-LA-MRSA. This suggest that infection control practices for LA-MRSA may possibly be less stringent than for non-LA-MRSA.

SNPs identified as modulators of ECG traits in the general population do not markedly affect ECG traits during acute myocardial infarction nor ventricular fibrillation risk in this condition.

BACKGROUND: Ventricular fibrillation (VF) in the setting of acute ST elevation myocardial infarction (STEMI) is a leading cause of mortality. Although the risk of VF has a genetic component, the underlying genetic factors are largely unknown. Since heart rate and ECG intervals of conduction and repolarization during acute STEMI differ between patients who do and patients who do not develop VF, we investigated whether SNPs known to modulate these ECG indices in the general population also impact on the respective ECG indices during STEMI and on the risk of VF. METHODS AND RESULTS: The study population consisted of participants of the Arrhythmia Genetics in the NEtherlandS (AGNES) study, which enrols patients with a first STEMI that develop VF (cases) and patients that do not develop VF (controls). SNPs known to impact on RR interval, PR interval, QRS duration or QTc interval in the general population were tested for effects on the respective STEMI ECG indices (stage 1). Only those showing a (suggestive) significant association were tested for association with VF (stage 2). On average, VF cases had a shorter RR and a longer QTc interval compared to non-VF controls. Eight SNPs showed a trend for association with the respective STEMI ECG indices. Of these, three were also suggestively associated with VF. CONCLUSIONS: RR interval and ECG indices of conduction and repolarization during acute STEMI differ between patients who develop VF and patients who do not. Although the effects of the SNPs on ECG indices during an acute STEMI seem to be similar in magnitude and direction as those found in the general population, the effects, at least in isolation, are too small to explain the differences in ECGs between cases and controls and to determine risk of VF.

Mild-to-moderate kidney dysfunction and the risk of sudden cardiac death in the setting of acute myocardial infarction.

BACKGROUND: Although end-stage renal disease is known to elevate the risk of sudden cardiac death (SCD), the role of less severe renal impairment in SCD is unclear. OBJECTIVE: The purpose of this study was to examine the association between mild-to-moderate renal impairment and first ischemic ventricular fibrillation (VF). METHODS: Renal function in patients included in the Arrhythmia Genetics in the NEtherlands Study (AGNES) were compared. Cases (n = 337, age 56 ± 1 year, 80% men) were defined as patients who had survived VF at the time of their first acute ST elevation myocardial infarction (STEMI), and controls (n = 339, age 58 ± 1 years, 80% men) were defined as those without VF during their first acute STEMI. Estimated glomerular filtration rate (eGFR) at the time of acute STEMI was computed using the 4-variable Modification of Diet in Renal Disease equation. RESULTS: At eGFR less than 105 mL/min, a decrease in eGFR was associated with elevated odds of developing VF during STEMI. The association was essentially flat at eGFR levels >105 mL/min. The lowest eGFR quintile was associated with a >6-fold increase in odds of developing VF compared to the fourth quintile. This association between eGFR and VF at the time of STEMI remained significant after adjusting for potential confounders including electrolyte levels. CONCLUSION: Mild-to-moderate kidney dysfunction is associated with a significantly elevated risk of VF in the setting of acute STEMI. Further studies are needed to investigate the precise mechanisms by which mild kidney function results in VF.

Antimicrobial drug use and resistance in Europe.

Our study confronts the use of antimicrobial agents in ambulatory care with the resistance trends of 2 major pathogens, Streptococcus pneumoniae and Escherichia coli, in 21 European countries in 2000-2005 and explores whether the notion that antimicrobial drug use determines resistance can be supported by surveillance data at national aggregation levels. The data obtained from the European Surveillance of Antimicrobial Consumption and the European Antimicrobial Resistance Surveillance System suggest that variation of consumption coincides with the occurrence of resistance at the country level. Linear regression analysis showed that the association between antimicrobial drug use and resistance was specific and robust for 2 of 3 compound pathogen combinations, stable over time, but not sensitive enough to explain all of the observed variations. Ecologic studies based on routine surveillance data indicate a relation between use and resistance and support interventions designed to reduce antimicrobial drug consumption at a national level in Europe.

Prevalence of methicillin-resistant Staphylococcus aureus (MRSA) in invasive isolates from southern and eastern Mediterranean countries.

OBJECTIVES: Efforts aimed at curtailing the ever increasing spread of methicillin-resistant Staphylococcus aureus (MRSA) require effective information of its epidemiology. However, knowledge about the situation in southern and eastern countries of the Mediterranean is incomplete since reports have been sporadic and difficult to compare. METHODS: Over a 36 month period from 2003 to 2005, the ARMed project collected more than 5000 susceptibility test results of invasive isolates of S. aureus from blood cultures routinely processed within participating laboratories servicing 62 hospitals situated in Algeria, Cyprus, Egypt, Jordan, Lebanon, Malta, Morocco, Tunisia and Turkey. RESULTS: Overall, the median MRSA proportion was 39% (interquartile range: 27.1% to 51.1%). The highest proportions of MRSA were reported by Jordan, Egypt and Cyprus, where more than 50% of the invasive isolates were methicillin-resistant. Considerable variation was identified in the proportion of MRSA in hospitals within the same country. CONCLUSIONS: It appears that most of the countries in the Mediterranean region are experiencing a surge in MRSA infections. This requires a greater focus to identify relevant drivers of resistance and implement effective practices in order to address them, especially improved infection control and antibiotic consumption practices.

Emergence of methicillin-resistant Staphylococcus aureus of animal origin in humans.

In 2003 in the Netherlands, a new methicillin-resistant Staphylococcus aureus (MRSA) strain emerged that could not be typed with Sma1 pulsed-field gel electrophoresis (NT-MRSA). The association of NT-MRSA in humans with a reservoir in animals was investigated. The frequency of NT-MRSA increased from 0% in 2002 to >21% after intensified surveillance was implemented in July 2006. Geographically, NT-MRSA clustered with pig farming. A case-control study showed that carriers of NT-MRSA were more often pig or cattle farmers (pig farmers odds ratio [OR] 12.2, 95% confidence interval [CI] 3.1-48.6; cattle farmers OR 19.7, 95% CI 2.3-169.5). Molecular typing showed that the NT-MRSA strains belonged to a new clonal complex, ST 398. This study shows that MRSA from an animal reservoir has recently entered the human population and is now responsible for >20% of all MRSA in the Netherlands.

Trends of penicillin and erythromycin resistance among invasive Streptococcus pneumoniae in Europe.

OBJECTIVES: To forecast trends in resistance to penicillin and erythromycin among Streptococcus pneumoniae in Europe. METHODS: Since 1999, the European Antimicrobial Resistance Surveillance System (EARSS) has collected routine antimicrobial susceptibility test results of S. pneumoniae. To observe and predict changes of reduced susceptibility over time, we used a multinomial logistic regression model. RESULTS: Large variations in penicillin and erythromycin non-susceptibility were observed between countries, and reduced susceptibility to erythromycin (17%) has become more frequent than reduced susceptibility to penicillin (10%) in Europe overall. An overall decrease in single penicillin non-susceptibility, but an increase in dual non-susceptibility was observed, indicating a shift of single penicillin to combined non-susceptibility with erythromycin. By 2006, the proportion of single erythromycin and dual non-susceptibility could increase to as much as 20.4% and 8.9%, respectively. CONCLUSIONS: Our results indicate that appropriately dosed beta-lactams for empirical therapy are still the treatment of choice, and that macrolides should be used with prudence.

Methicillin-resistant Staphylococcus aureus in Europe, 1999-2002.

We explored the variation in proportions of methicillin-resistant Staphylococcus aureus (MRSA) between and within countries participating in the European Antimicrobial Resistance Surveillance System and temporal trends in its occurrence. This system collects routine antimicrobial susceptibility tests for S. aureus. We examined data collected from January 1999 through December 2002 (50,759 isolates from 495 hospitals in 26 countries). MRSA prevalence varied almost 100-fold, from <1% in northern Europe to >40% in southern and western Europe. MRSA proportions significantly increased in Belgium, Germany, Ireland, the Netherlands, and the United Kingdom, and decreased in Slovenia. Within countries, MRSA proportions varied between hospitals with highest variance in countries with a prevalence of 5% to 20%. The observed trends should stimulate initiatives to control MRSA at national, regional, and hospital levels. The large differences between hospitals indicate that efforts may be most effective at regional and hospital levels.

Different levels of genetic homogeneity in vancomycin-resistant and -susceptible Enterococcus faecium isolates from different human and animal sources analyzed by amplified-fragment length polymorphism.

The genetic relationship among fecal vancomycin-resistant Enterococcus faecium (VREF) and vancomycin-susceptible E. faecium (VSEF) isolates (n = 178) from the same populations of pigs, human healthy volunteers, and hospitalized patients (from The Netherlands) and chickens (from The Netherlands and Greece) was studied by amplified-fragment length polymorphism (AFLP). The majority of VREF isolates from pigs, healthy volunteers, and hospitalized patients grouped together (genetic similarity, >or=65%). In a previous AFLP study by our group the VREF isolates from hospitalized patients grouped separately, most likely because these were clinical and not fecal isolates as in the present study. Furthermore, VSEF isolates from humans and pigs were found much more genetically diverse than VREF isolates, whereas VREF and VSEF isolates from chickens clustered together in a separate genogroup (genetic similarity, >or=65%), a pattern clearly distinct from the patterns for human and pig isolates. The present study suggests that pigs are a more important source of VREF for humans than chickens and that human- and pig-derived VSEF isolates seem much more heterogeneous than VREF isolates.