Eumycetoma causative agents: A systematic review to inform the World Health Organization priority list of fungal pathogens.

The World Health Organization, in response to the growing burden of fungal disease, established a process to develop a fungal priority pathogens list. This systematic review aimed to evaluate the epidemiology and impact of eumycetoma. PubMed and Web of Science were searched to identify studies published between 1 January 2011 and 19 February 2021. Studies reporting on mortality, inpatient care, complications and sequelae, antifungal susceptibility, risk factors, preventability, annual incidence, global distribution, and emergence during the study time frames were selected. Overall, 14 studies were eligible for inclusion. Morbidity was frequent with moderate to severe impairment of quality of life in 60.3%, amputation in up to 38.5%, and recurrent or long-term disease in 31.8%-73.5% of patients. Potential risk factors included male gender (56.6%-79.6%), younger age (11-30 years; 64%), and farming occupation (62.1%-69.7%). Mycetoma was predominantly reported in Sudan, particularly in central Sudan (37%-76.6% of cases). An annual incidence of 0.1/100 000 persons and 0.32/100 000 persons/decade was reported in the Philippines and Uganda, respectively. In Uganda, a decline in incidence from 3.37 to 0.32/100 000 persons between two consecutive 10-year periods (2000-2009 and 2010-2019) was detected. A community-based, multi-pronged prevention programme was associated with a reduction in amputation rates from 62.8% to 11.9%. With the pre-specified criteria, no studies of antifungal drug susceptibility, mortality, and hospital lengths of stay were identified. Future research should include larger cohort studies, greater drug susceptibility testing, and global surveillance to develop evidence-based treatment guidelines and to determine more accurately the incidence and trends over time.

Mucorales: A systematic review to inform the World Health Organization priority list of fungal pathogens.

The World Health Organization, in response to the growing burden of fungal disease, established a process to develop a fungal priority pathogens list (FPPL). This systematic review aimed to evaluate the epidemiology and impact of invasive fungal disease due to Mucorales. PubMed and Web of Science were searched to identify studies published between January 1, 2011 and February 23, 2021. Studies reporting on mortality, inpatient care, complications and sequelae, antifungal susceptibility, risk factors, preventability, annual incidence, global distribution, and emergence during the study time frames were selected. Overall, 24 studies were included. Mortality rates of up to 80% were reported. Antifungal susceptibility varied across agents and species, with the minimum inhibitory concentrations lowest for amphotericin B and posaconazole. Diabetes mellitus was a common risk factor, detected in 65%-85% of patients with mucormycosis, particularly in those with rhino-orbital disease (86.9%). Break-through infection was detected in 13.6%-100% on azole or echinocandin antifungal prophylaxis. The reported prevalence rates were variable, with some studies reporting stable rates in the USA of 0.094-0.117/10 000 discharges between 2011 and 2014, whereas others reported an increase in Iran from 16.8% to 24% between 2011 and 2015. Carefully designed global surveillance studies, linking laboratory and clinical data, are required to develop clinical breakpoints to guide antifungal therapy and determine accurate estimates of complications and sequelae, annual incidence, trends, and global distribution. These data will provide robust estimates of disease burden to refine interventions and better inform future FPPL.

Talaromyces marneffei, Coccidioides species, and Paracoccidioides species-a systematic review to inform the World Health Organization priority list of fungal pathogens.

The World Health Organization, in response to the growing burden of fungal disease, established a process to develop a fungal pathogen priority list. This systematic review aimed to evaluate the epidemiology and impact of infections caused by Talaromyces marneffei, Coccidioides species, and Paracoccidioides species. PubMed and Web of Sciences databases were searched to identify studies published between 1 January 2011 and 23 February 2021 reporting on mortality, complications and sequelae, antifungal susceptibility, preventability, annual incidence, and trends. Overall, 25, 17, and 6 articles were included for T. marneffei, Coccidioides spp. and Paracoccidioides spp., respectively. Mortality rates were high in those with invasive talaromycosis and paracoccidioidomycosis (up to 21% and 22.7%, respectively). Hospitalization was frequent in those with coccidioidomycosis (up to 84%), and while the duration was short (mean/median 3-7 days), readmission was common (38%). Reduced susceptibility to fluconazole and echinocandins was observed for T. marneffei and Coccidioides spp., whereas >88% of T. marneffei isolates had minimum inhibitory concentration values ≤0.015 µg/ml for itraconazole, posaconazole, and voriconazole. Risk factors for mortality in those with talaromycosis included low CD4 counts (odds ratio 2.90 when CD4 count <200 cells/µl compared with 24.26 when CD4 count <50 cells/µl). Outbreaks of coccidioidomycosis and paracoccidioidomycosis were associated with construction work (relative risk 4.4-210.6 and 5.7-times increase, respectively). In the United States of America, cases of coccidioidomycosis increased between 2014 and 2017 (from 8232 to 14 364/year). National and global surveillance as well as more detailed studies to better define sequelae, risk factors, outcomes, global distribution, and trends are required.

Candida glabrata (Nakaseomyces glabrata): A systematic review of clinical and microbiological data from 2011 to 2021 to inform the World Health Organization Fungal Priority Pathogens List.

Recognising the growing global burden of fungal infections, the World Health Organization (WHO) established an advisory group consisting of experts in fungal diseases to develop a Fungal Priority Pathogen List. Pathogens were ranked based on their research and development needs and perceived public health importance using a series of global surveys and pathogen characteristics derived from systematic reviews. This systematic review evaluates the features and global impact of invasive disease caused by Candida glabrata (Nakaseomyces glabrata). PubMed and Web of Science were searched for studies reporting on mortality, morbidity (hospitalization and disability), drug resistance (including isolates from sterile and non-sterile sites, since these reflect the same organisms causing invasive infections), preventability, yearly incidence, diagnostics, treatability, and distribution/emergence in the last 10 years. Candida glabrata (N. glabrata) causes difficult-to-treat invasive infections, particularly in patients with underlying conditions such as immunodeficiency, diabetes, or those who have received broad-spectrum antibiotics or chemotherapy. Beyond standard infection prevention and control measures, no specific preventative measures have been described. We found that infection is associated with high mortality rates and that there is a lack of data on complications and sequelae. Resistance to azoles is common and well described in echinocandins-in both cases, the resistance rates are increasing. Candida glabrata remains mostly susceptible to amphotericin and flucytosine. However, the incidence of the disease is increasing, both at the population level and as a proportion of all invasive yeast infections, and the increases appear related to the use of antifungal agents.

Features and global impact of invasive fungal infections caused by Pneumocystis jirovecii: A systematic review to inform the World Health Organization fungal priority pathogens list.

This systematic review evaluates the current global impact of invasive infections caused by Pneumocystis jirovecii (principally pneumonia: PJP), and was carried out to inform the World Health Organization Fungal Priority Pathogens List. PubMed and Web of Science were used to find studies reporting mortality, inpatient care, complications/sequelae, antifungal susceptibility/resistance, preventability, annual incidence, global distribution, and emergence in the past 10 years, published from January 2011 to February 2021. Reported mortality is highly variable, depending on the patient population: In studies of persons with HIV, mortality was reported at 5%-30%, while in studies of persons without HIV, mortality ranged from 4% to 76%. Risk factors for disease principally include immunosuppression from HIV, but other types of immunosuppression are increasingly recognised, including solid organ and haematopoietic stem cell transplantation, autoimmune and inflammatory disease, and chemotherapy for cancer. Although prophylaxis is available and generally effective, burdensome side effects may lead to discontinuation. After a period of decline associated with improvement in access to HIV treatment, new risk groups of immunosuppressed patients with PJP are increasingly identified, including solid organ transplant patients.

Genomic epidemiology of Staphylococcus aureus isolated from bloodstream infections in South America during 2019 supports regional surveillance.

Staphylococcus aureus remains one of the leading causes of infections worldwide and a common cause of bacteraemia. However, studies documenting the epidemiology of S. aureus in South America using genomics are scarce. We hereby report on the largest genomic epidemiology study to date of both methicillin-resistant S. aureus (MRSA) and methicillin-susceptible S. aureus (MSSA) in South America, conducted by the StaphNET-SA network. We characterised 404 genomes recovered from a prospective observational study of S. aureus bacteraemia in 58 hospitals from Argentina, Bolivia, Brazil, Paraguay and Uruguay between April and October 2019. We show that a minority of S. aureus isolates are phenotypically multi-drug resistant (5.2%), but more than a quarter are resistant to macrolide-lincosamide-streptogramin B (MLSb). MSSA were more genetically diverse than MRSA. Lower rates of associated antimicrobial resistance in community-associated(CA)-MRSA versus hospital-associated (HA)-MRSA were found in association with three S. aureus genotypes dominating the MRSA population: CC30-MRSA-IVc-t019-lukS/F-PV+, CC5-MRSA-IV-t002-lukS/F-PV- and CC8-MRSA-IVc-t008-lukS/F-PV+-COMER+. These are historically from a CA origin, carry on average fewer antimicrobial resistance determinants, and often lack key virulence genes. Surprisingly, CC398-MSSA-t1451-lukS/F-PV- related to the CC398 human-associated lineage is widely disseminated throughout the region, and is described here for the first time as the most prevalent MSSA lineage in South America. Moreover, CC398 strains carrying ermT (largely responsible for the MLSb resistance rates of MSSA strains: inducible iMLSb phenotype) and sh_fabI (related to triclosan resistance) were recovered from both CA and HA origin. The frequency of MRSA and MSSA lineages differed between countries but the most prevalent S. aureus genotypes are high-risk clones widely distributed in the South American region without a clear country-specific phylogeographical structure. Therefore, our findings underline the need for continuous genomic surveillance by regional networks such as StaphNET-SA. This article contains data hosted by Microreact.

Increased Detection of Carbapenemase-Producing Enterobacterales Bacteria in Latin America and the Caribbean during the COVID-19 Pandemic.

During 2020-2021, countries in Latin America and the Caribbean reported clinical emergence of carbapenemase-producing Enterobacterales that had not been previously characterized locally, increased prevalence of carbapenemases that had previously been detected, and co-production of multiple carbapenemases in some isolates. These increases were likely fueled by changes related to the COVID-19 pandemic, including empirical antibiotic use for potential COVID-19-related bacterial infections and healthcare limitations resulting from the rapid rise in COVID-19 cases. Strengthening antimicrobial resistance surveillance, epidemiologic research, and infection prevention and control programs and antimicrobial stewardship in clinical settings can help prevent emergence and transmission of carbapenemase-producing Enterobacterales.

Peptidome profiling for the immunological stratification in sepsis: a proof of concept study.

Sepsis has been called the graveyard of pharmaceutical companies due to the numerous failed clinical trials. The lack of tools to monitor the immunological status in sepsis constrains the development of therapies. Here, we evaluated a test based on whole plasma peptidome acquired by MALDI-TOF-mass spectrometer and machine-learning algorithms to discriminate two lipopolysaccharide-(LPS) induced murine models emulating the pro- and anti-inflammatory/immunosuppression environments that can be found during sepsis. The LPS group was inoculated with a single high dose of LPS and the IS group was subjected to increasing doses of LPS, to induce proinflammatory and anti-inflammatory/immunosuppression profiles respectively. The LPS group showed leukopenia and higher levels of cytokines and tissue damage markers, and the IS group showed neutrophilia, lymphopenia and decreased humoral response. Principal component analysis of the plasma peptidomes formed discrete clusters that mostly coincided with the experimental groups. In addition, machine-learning algorithms discriminated the different experimental groups with a sensitivity of 95.7% and specificity of 90.9%. Data reveal the potential of plasma fingerprints analysis by MALDI-TOF-mass spectrometry as a simple, speedy and readily transferrable method for sepsis patient stratification that would contribute to therapeutic decision-making based on their immunological status.

Antibiotic resistance and associated resistance determinants in different Salmonella enterica serovars isolated from pigs in Argentina.

Background and Aim: Salmonellosis is one of the most common foodborne diseases in the world, and the increasing antibiotic resistance in Salmonella enterica subsp. enterica recovered from food animals constitutes an important risk from a One Health approach. This study aimed to characterize antibiotic resistance and some of its associated resistance determinants in different S. enterica serovars isolated from pigs in Argentina. Materials and Methods: A retrospective study was conducted on Salmonella strains isolated between 2011 and 2015 from pigs in the Pampean region of Argentina. The antimicrobial susceptibility patterns to 21 antimicrobials and some antibiotic resistance determinants were characterized in 55 Salmonella isolates, representing 58 farms. Results: We identified 56% (n=30) of the strains as multidrug-resistant, where resistance to tetracycline (62%, n=34), ampicillin (53%, n=29), nalidixic acid (53%, n=29), chloramphenicol (33%, n=18), and trimethoprim-sulfamethoxazole (31%, n=17) was most common. The wide range of resistance to ampicillin correlates with the presence of TEM type ß-lactamases in the strains. However, high susceptibility was found in the new generation of ß-lactams. Fluoroquinolone resistance is a major concern. Most strains with decreased susceptibility to ciprofloxacin showed gyrA mutations and plasmid-mediated quinolone resistance gene qnrB. Conclusion: Here, we identified broad resistance to some antibiotics frequently used in human therapeutics and several easily transferable resistance mechanisms that could endanger public health.

Effects of screening strategies to detect carbapenem-resistant gram-negative bacteria: A systematic review.

OBJECTIVE: This systematic review aims to summarize the evidence on the effects of screening strategies to detect carbapenem-resistant gram-negative bacteria (Enterobacteriaceae, Acinetobacter baumannii, and Pseudomonas aeruginosa). METHODS: Eligible studies were randomized trials, non-randomized controlled trials, controlled before-after studies, and interrupted time series. We conducted searches in CENTRAL, PUBMED, Embase, Epistemonikos, and in multiple databases available in the Virtual Health Library (LILACS, Scielo, WHO IBECS, and PAHO IBECS). All the searches covered the period until 4 June 2021. No date or language restrictions were applied. Two reviewers independently evaluated potentially eligible studies according to predefined selection criteria, and extracted data on study characteristics, methods, outcomes, and risk of bias, using a predesigned standardized form. When possible, we intended to conduct meta-analyses using a random-effect model. We assessed the certainty of the evidence (CoE) and summarized the results using the GRADE approach. RESULTS: Our search strategy yielded 57,451 references. No randomized trials were identified. Sixteen studies (one controlled before-after study and 15 interrupted time series) met our inclusion criteria and were included in the review. Most studies were conducted in tertiary care general hospitals from the United States, Europe, and Asia. Eleven studies included adult patients hospitalized in general wards and intensive care units, one was carried out in a neonatal intensive care unit, two in hematology or oncology units, and one in a solid organ transplantation department. Eleven studies were conducted in the setting of an outbreak. Regarding the detection strategy used, all studies included screening strategies for high-risk patients at the moment of admission and 7 studies reported a contact surveillance strategy. Most studies were conducted in settings where infection prevention and control measures were concomitantly installed or reinforced. Data were not suitable for meta-analysis, so the results were presented as a narrative synthesis. Most studies showed a decline in the prevalence of both infection and colonization rates after the implementation of a policy of active surveillance, but the CoE is low. Screening strategies may result in little to no difference in the risk of all-cause mortality and the length of hospital stay. CONCLUSIONS: Existing evidence may favor the use of surveillance culture to carbapenem-resistant gram-negative bacteria, but its quality is poor, so solid conclusions cannot be drawn. Well-conducted randomized trials or high-quality quasi-experimental studies are needed to improve the certainty of the existing evidence. These studies should assess the effect of the addition of screening strategies as a single intervention and measure clinically important outcomes such as infection, length of hospital stay, and mortality.

Emergence of MDR invasive Neisseria meningitidis in El Salvador, 2017-19.

BACKGROUND: Invasive meningococcal disease (IMD) is an acute, highly transmissible and potentially fatal disease caused by Neisseria meningitidis. Prompt antimicrobial therapy and prophylaxis are recommended, where penicillin or ciprofloxacin are the available choices. However, the emergence of resistant isolates of N. meningitidis poses a challenge for antimicrobial therapy. OBJECTIVES: To describe the clinical, epidemiological and biological characteristics of six penicillin- and ciprofloxacin-resistant, culture-confirmed IMD cases reported in El Salvador, Central America, between 2017 and 2019. METHODS: Following the detection of six patients presenting with IMD in El Salvador, clinical data were collected and epidemiological action plans conducted. Isolates were subjected to antimicrobial susceptibility testing by broth microdilution and WGS for genotyping and molecular characterization analysis, including phylogeny comparison with global sequences available from public databases. RESULTS: A total of six IMD cases caused by N. meningitidis serogroup Y, resistant to both penicillin (MIC >8.0 mg/L) and ciprofloxacin (MIC 0.125 mg/L), were detected from 2017 to 2019. Genomic analysis showed that penicillin resistance was mediated by the production of ß-lactamase ROB-1. Ciprofloxacin resistance was attributed to an amino acid substitution in DNA gyrase (T91I). All isolates were classified as ST3587, clonal complex 23, and were genetically highly similar, based on core-genome SNP analysis. CONCLUSIONS: To the best of our knowledge, we report the first cases of MDR N. meningitidis causing IMD in Latin America. Our findings highlight the emergence of this potential public health threat, with a profound impact on the efficacy of IMD treatment and prophylaxis protocols.

WHO global antimicrobial resistance surveillance for Neisseria gonorrhoeae 2017-18: a retrospective observational study.

BACKGROUND: Gonorrhoea and antimicrobial resistance (AMR) in Neisseria gonorrhoeae are major health concerns globally. Increased global surveillance of gonococcal AMR is essential. We aimed to describe the 2017-18 data from WHO's global gonococcal AMR surveillance, and to discuss priorities essential for the effective management and control of gonorrhoea. METHODS: We did a retrospective observational study of the AMR data of gonococcal isolates reported to WHO by 73 countries in 2017-18. WHO recommends that each country collects at least 100 gonococcal isolates per year, and that quantitative methods to determine the minimum inhibitory concentration of antimicrobials, interpreted by internationally standardised resistance breakpoints, are used. FINDINGS: In 2017-18, 73 countries provided AMR data for one or more drug. Decreased susceptibility or resistance to ceftriaxone was reported by 21 (31%) of 68 reporting countries and to cefixime by 24 (47%) of 51 reporting countries. Resistance to azithromycin was reported by 51 (84%) of 61 reporting countries and to ciprofloxacin by all 70 (100%) reporting countries. The annual proportion of decreased susceptibility or resistance across countries was 0-21% to ceftriaxone and 0-22% to cefixime, and that of resistance was 0-60% to azithromycin and 0-100% to ciprofloxacin. The number of countries reporting gonococcal AMR and resistant isolates, and the number of examined isolates, have increased since 2015-16. Surveillance remains scarce in central America and the Caribbean and eastern Europe, and in the WHO African, Eastern Mediterranean, and South-East Asian regions. INTERPRETATION: In many countries, ciprofloxacin resistance was exceedingly high, azithromycin resistance was increasing, and decreased susceptibility or resistance to ceftriaxone and cefixime continued to emerge. WHO's global surveillance of gonococcal AMR needs to expand internationally to provide imperative data for national and international management guidelines and public health policies. Improved prevention, early diagnosis, treatment of index patients and partners, enhanced surveillance (eg, infection, AMR, treatment failures, and antimicrobial use or misuse), and increased knowledge on antimicrobial selection, stewardship, and pharmacokinetics or pharmacodynamics are essential. The development of rapid, accurate, and affordable point-of-care gonococcal diagnostic tests, new antimicrobials, and gonococcal vaccines is imperative. FUNDING: None.

[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.

OXA-48 Carbapenemase in Klebsiella pneumoniae Sequence Type 307 in Ecuador.

Antibiotic resistance is on the rise, leading to an increase in morbidity and mortality due to infectious diseases. Klebsiella pneumoniae is a Gram-negative bacterium that causes bronchopneumonia, abscesses, urinary tract infection, osteomyelitis, and a wide variety of infections. The ubiquity of this microorganism confounds with the great increase in antibiotic resistance and have bred great concern worldwide. K. pneumoniae sequence type (ST) 307 is a widespread emerging clone associated with hospital-acquired infections, although sporadic community infections have also been reported. The aim of our study is to describe the first case of Klebsiella pneumoniae (ST) 307 harboring the blaOXA-48-like gene in Ecuador. We characterized a new plasmid that carry OXA-48 and could be the source of future outbreaks. The strain was recovered from a patient with cancer previously admitted in a Ukrainian hospital, suggesting that this mechanism of resistance could be imported. These findings highlight the importance of programs based on active molecular surveillance for the intercontinental spread of multidrug-resistant microorganisms with emergent carbapenemases.

[Latin American consensus to define, categorize, and report multidrug-resistant, extensively drug-resistant, or pandrug-resistant pathogensConsenso latino-americano para definição, categorização e notificação de patógenos multirresistentes, com resistência ampliada ou panresistentes]. / Consenso latinoamericano para definir, categorizar y notificar patógenos multirresistentes, con resistencia extendida o panresistentes.

This document presents a Latin American consensus to standardize definitions of different levels of antimicrobial resistance in bacteria of public health importance. Inclusion and exclusion criteria are described for antibiotics to include (availability, relevance, and existence of cut-off values) and for methodologies to use. Three gram-negative microorganisms with a great impact in the hospital environment (Klebsiella pneumoniae, Pseudomonas aeruginosa, and Acinetobacter spp.) were selected as a pilot proposal. The lack of cut-off values for certain antibiotics (e.g., tigecycline, fosfomycin, and colistin), crucial in treating infections caused by multi-drug resistant or extensively drug-resistant pathogens, led to the need to discuss and agree on provisional cut-off values for monitoring resistance to these drugs. The work team also addressed and reached consensus on easier-to-use alternative susceptibility tests, other than methods approved by international guidelines, for routine testing in clinical bacteriology laboratories. The main benefit of this document is to provide Latin American laboratories with a standardized and consensual framework for the identification and constant and unified surveillance of resistant microorganisms. The recommendations included in this document are the result of consensus among representatives of the national reference laboratories in the countries belonging to the Latin American Surveillance Network of Antimicrobial Resistance, coordinated by the Pan American Health Organization.

É apresentado um consenso latino-americano para padronizar a definição dos graus de resistência antimicrobiana em bactérias de importância em saúde pública. São descritos os critérios de inclusão e exclusão para os antibióticos a serem incluídos (disponibilidade, relevância e pontos de corte de sensibilidade) e metodologias a serem usadas. Como proposta-piloto, foram selecionados três microrganismos Gram-negativos de grande impacto no ambiente hospitalar (Klebsiella pneumoniae, Pseudomonas aeruginosa e Acinetobacter spp.). Diante da falta de pontos de corte para alguns antibióticos (como tigeciclina, fosfomicina e colistina), essenciais para o tratamento de infecções causadas por patógenos com multirresistência ou resistência ampliada, foram debatidos e aprovados pela maioria pontos de corte provisórios para a vigilância da resistência a estes fármacos. Também foi discutido e aprovado o uso de testes de suscetibilidade alternativos aos métodos aprovados pelas diretrizes internacionais, mais simples de serem realizados como testes de rotina nos laboratórios de bacteriologia clínica. A principal contribuição deste documento é oferecer aos laboratórios latino-americanos um sistema padronizado e consensual para a identificação de microrganismos resistentes e a vigilância contínua e uniforme destes patógenos. As recomendações aqui contidas foram feitas por consenso por representantes dos laboratórios nacionais de referência dos países que integram a Rede Latino-Americana de Vigilância da Resistência Antimicrobiana, coordenada pela Organização Pan-Americana da Saúde (OPAS).

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.

Consenso latinoamericano para definir, categorizar y notificar patógenos multirresistentes, con resistencia extendida o panresistentes

[RESUMEN]. Se presenta un consenso latinoamericano que permite estandarizar las definiciones de los diferentes niveles de resistencia a los antimicrobianos en bacterias de importancia en salud pública. Se describen los criterios de inclusión y exclusión para las metodologías a utilizar y para los antibióticos a incluir (por disponibilidad, relevancia y existencia de puntos de corte). Como propuesta piloto se eligieron tres microorganismos gramnegativos de gran impacto en el ambiente hospitalario (Klebsiella pneumoniae, Pseudomonas aeruginosa y Acinetobacter spp.). La falta de puntos de corte para ciertos antibióticos (por ejemplo, tigeciclina, fosfomicina y colistina), claves para el tratamiento de infecciones causadas por estos patógenos que presentan multirresistencia o resistencia extendida, llevó a la necesidad de discutir y consensuar puntos de corte provisorios para la vigilancia de la resistencia a estos fármacos. Se abordó y consensuó también el uso de pruebas de sensibilidad alternativas a los métodos aprobados por las guías internacionales, de aplicación más sencilla como pruebas de rutina en los laboratorios de bacteriología clínica. El principal beneficio de este documento es proporcionar a los laboratorios latinoamericanos un marco estandarizado y consensuado para la identificación y la vigilancia constante y unificada de microorganismos resistentes. Las recomendaciones incluidas en este documento son el resultado consensuado por los representantes de los laboratorios nacionales de referencia de los países que integran la Red Latinoamericana de Vigilancia de la Resistencia a los Antibióticos coordinada por la Organización Panamericana de la Salud

[ABSTRACT]. This document presents a Latin American consensus to standardize definitions of different levels of antimicrobial resistance in bacteria of public health importance. Inclusion and exclusion criteria are described for antibiotics to include (availability, relevance, and existence of cut-off values) and for methodologies to use. Three gram-negative microorganisms with a great impact in the hospital environment (Klebsiella pneumoniae, Pseudomonas aeruginosa, and Acinetobacter spp.) were selected as a pilot proposal. The lack of cut-off values for certain antibiotics (e.g., tigecycline, fosfomycin, and colistin), crucial in treating infections caused by multi-drug resistant or extensively drug-resistant pathogens, led to the need to discuss and agree on provisional cut-off values for monitoring resistance to these drugs. The work team also addressed and reached consensus on easier-to-use alternative susceptibility tests, other than methods approved by international guidelines, for routine testing in clinical bacteriology laboratories. The main benefit of this document is to provide Latin American laboratories with a standardized and consensual framework for the identification and constant and unified surveillance of resistant microorganisms. The recommendations included in this document are the result of consensus among representatives of the national reference laboratories in the countries belonging to the Latin American Surveillance Network of Antimicrobial Resistance, coordinated by the Pan American Health Organization.

[RESUMO]. É apresentado um consenso latino-americano para padronizar a definição dos graus de resistência antimicrobiana em bactérias de importância em saúde pública. São descritos os critérios de inclusão e exclusão para os antibióticos a serem incluídos (disponibilidade, relevância e pontos de corte de sensibilidade) e metodologias a serem usadas. Como proposta-piloto, foram selecionados três microrganismos Gram-negativos de grande impacto no ambiente hospitalar (Klebsiella pneumoniae, Pseudomonas aeruginosa e Acinetobacter spp.). Diante da falta de pontos de corte para alguns antibióticos (como tigeciclina, fosfomicina e colistina), essenciais para o tratamento de infecções causadas por patógenos com multirresistência ou resistência ampliada, foram debatidos e aprovados pela maioria pontos de corte provisórios para a vigilância da resistência a estes fármacos. Também foi discutido e aprovado o uso de testes de suscetibilidade alternativos aos métodos aprovados pelas diretrizes internacionais, mais simples de serem realizados como testes de rotina nos laboratórios de bacteriologia clínica. A principal contribuição deste documento é oferecer aos laboratórios latino-americanos um sistema padronizado e consensual para a identificação de microrganismos resistentes e a vigilância contínua e uniforme destes patógenos. As recomendações aqui contidas foram feitas por consenso por representantes dos laboratórios nacionais de referência dos países que integram a Rede Latino-Americana de Vigilância da Resistência Antimicrobiana, coordenada pela Organização Pan-Americana da Saúde (OPAS).