New insights on mcr-1-harboring plasmids from human clinical Escherichia coli isolates.

Mobile colistin resistance (mcr) genes were described recently in Gram-negative bacteria including carbapenem-resistant Enterobacterales. There are ten mcr genes described in different Gram-negative bacteria, however, Escherichia coli harboring mcr-1 gene is by far the most frequent combination. In Argentina, mcr-1 gene was characterized only on plasmids belonging to IncI2 group. The aim of this work was to get new insights of mcr-1-harboring plasmids from E. coli. Eight E. coli isolates from a larger collection of 192 clinical E. coli isolates carrying the mcr-1 gene were sequenced using next generation technologies. Three isolates belonged to ST131 high-risk clone, and five to single ST, ST38, ST46, ST226, ST224, and ST405. Eight diverse mcr-1-harboring plasmids were analyzed: IncI2 (1), IncX4 (3), IncHI2/2A (3) and a hybrid IncFIA/HI1A/HI1B (1) plasmid. Plasmids belonging to the IncI2 (n = 1) and IncX4 (n = 3) groups showed high similarity with previously described plasmids. Two IncHI2/HI2A plasmids, showed high identity between them, while the third, showed several differences including additional resistance genes like tet(A) and floR. One IncFIA/H1A/H1B hybrid plasmid was characterized, highly similar to pSRC27-H, a prototype plasmid lacking mcr genes. mcr-1.5 variant was found in four plasmids with three different Inc groups: IncI2, IncHI2/HI2A and the hybrid FIA/HI1A/HI1B plasmid. mcr-1.5 variant is almost exclusively described in our country and with a high frequency. In addition, six E. coli isolates carried three allelic variants codifying for CTX-M-type extended-spectrum-ß-lactamases: blaCTX-M-2 (3), blaCTX-M-65 (2), and blaCTX-M-14 (1). It is the first description of mcr-1 harboring plasmids different to IncI2 group in our country. These results represents new insights about mcr-1 harboring plasmids recovered from E. coli human samples from Argentina, showing different plasmid backbones and resistance gene combinations.

Opportunities and challenges in antimicrobial resistance policy including animal production systems and humans across stakeholders in Argentina: a context and qualitative analysis.

INTRODUCTION: Gaps in antimicrobial resistance (AMR) surveillance and control, including implementation of national action plans (NAPs), are evident internationally. Countries' capacity to translate political commitment into action is crucial to cope with AMR at the human-animal-environment interface. METHODS: We employed a two-stage process to understand opportunities and challenges related to AMR surveillance and control at the human-animal interface in Argentina. First, we compiled the central AMR policies locally and mapped vital stakeholders around the NAP and the national commission against bacterial resistance. Second, we conducted qualitative interviews using a semistructured questionnaire covering stakeholders' understanding and progress towards AMR and NAP. We employed a mixed deductive-inductive approach and used the constant comparative analysis method. We created categories and themes to cluster subthemes and determined crucial relationships among thematic groups. RESULTS: Crucial AMR policy developments have been made since 1969, including gradually banning colistin in food-producing animals. In 2023, a new government decree prioritised AMR following the 2015 NAP launch. Our qualitative analyses identified seven major themes for tackling AMR: (I) Cultural factors and sociopolitical country context hampering AMR progress, (II) Fragmented governance, (III) Antibiotic access and use, (IV) AMR knowledge and awareness throughout stakeholders, (V) AMR surveillance, (VI) NAP efforts and (VII) External drivers. We identified a fragmented structure of the food production chain, poor cross-coordination between stakeholders, limited surveillance and regulation among food-producing animals and geographical disparities over access, diagnosis and treatment. The country is moving to integrate animal and food production into its surveillance system, with most hospitals experienced in monitoring AMR through antimicrobial stewardship programmes. CONCLUSION: AMR accountability should involve underpinning collaboration at different NAP implementation levels and providing adequate resources to safeguard long-term sustainability. Incorporating a multisectoral context-specific approach relying on different One Health domains is crucial to strengthening local AMR surveillance.

Resistencia Primaria de HIV-1: estado de situación en Argentina: [revisión] / Primary resistance of HIV-1 in Argentina: state of the art: [review]

La transmisión de virus resistentes (TVR, o resistencia primaria) a individuos no expuestos a drogas antirretrovirales (naive), puede ser muy variable entre distintas regiones y es función de múltiples factores. En general, la TVR es máxima en regiones con acceso universal al tratamiento antirretroviral (TARV) por más de 20 años, como Estados Unidos y Europa. En Sudamérica, los índices de TVR eran < 5% al comienzo de la década, observándose actualmente niveles mayores, aparentemente estables, pero aún inferiores a los de Estados Unidos y Europa, y con mayor prevalencia de resistencia a inhibidores no-nucleosídicos de la transcriptasa reversa (INNTRs). En Argentina, la prevalencia de TVR está entre 3-6%, en población naive, y entre 7-8%, en infecciones recientes, pudiendo ser mayor en poblaciones más vulnerables al HIV-1, como trabajadores sexuales (13 %). La gran mayoría de los perfiles mutacionales de resistencia detectados contiene sólo 1-2 mutaciones marcadoras de TVR, y las más frecuentemente detectadas son: K 103N(aproximadamente 50% de los casos resistentes), M41L, M184V, V82A/S, M461/L, L90M, G190A, T215T, 154V y revertantes de T215Y/F. El impacto de la TVR en el TARV inicial parece ser cada vez más relevante, y se traduce en una reducción significativa de la respuesta virológica. Sin embargo, este efecto no se observa si la elección del TARV está guiada por monitoreo de resistencia basal. Los esquemas basados en INNTRs son más sensibles a la presencia de TVR y las variantes resistentes a INNTRs pueden mantener el impacto sobre la respuesta virológica aún a muy bajas frecuencias, no detectables por secuenciación poblacional.

The transmission of a drug-resistant virus (TDR, or primary resistance) to individuals not previously exposed to antiretroviral drugs (naive subjects) may be highly variable among different regions and is a function of a multitude of factors. As a general estimate, TVR is higher in those regions where antiretroviral therapy (ART) has been widely available for more than 20 years like USA and Europe. At the beginning of the last decade, the TDR rates were lower than 5% in South America but nowadays they have risen to an apparently steady level that is still lower than those from USA and Europe. Resistance to non-nucleoside reverse transcriptase inhibitors (NNRTls) is higher than to other drugs in South America. In Argentina, the TDR prevalence is about e-6% in naive populations and 7-8% in recent infections but it may be higher among populations at risks like sex workers (13%). Most of the detected resistance mutational patterns harbored 1-2 TDR mutations. The TDR mutations more frequently detected were: K103N (aprox 50% of resistant cases), M41L, M184V, V82A/S, M461/L, L90M, G190A, T215Y, 154V and T215Y/F revertants. The TDR impact on first-line ART seems more relevant leading to a significant reduction in virologic response. However, guided antiretroviral therapy based on baseline resistance testing can abrogate this limitation. NNRTI-based regimens are more sensitive to the presence of TDR and NNRTI-resistant variants may retain their impact on virologic response even if present at very low frequencies below the detection limit by bulk sequencing.