Actualización sobre la resistencia antimicrobiana en instituciones de salud de nivel III y IV en Colombia entre enero del 2018 y diciembre del 2021

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

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

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

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

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

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

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

Molecular Mechanisms of Resistance to Ceftazidime/Avibactam in Clinical Isolates of Enterobacterales and Pseudomonas aeruginosa in Latin American Hospitals.

Ceftazidime-avibactam (CZA) is the combination of a third-generation cephalosporin and a new non-ß-lactam ß-lactamase inhibitor capable of inactivating class A, C, and some D ß-lactamases. From a collection of 2,727 clinical isolates of Enterobacterales (n = 2,235) and P. aeruginosa (n = 492) that were collected between 2016 and 2017 from five Latin American countries, we investigated the molecular resistance mechanisms to CZA of 127 (18/2,235 [0.8%] Enterobacterales and 109/492 [22.1%] P. aeruginosa). First, by qPCR for the presence of genes encoding KPC, NDM, VIM, IMP, OXA-48-like, and SPM-1 carbapenemases, and second, by whole-genome sequencing (WGS). From the CZA-resistant isolates, MBL-encoding genes were detected in all 18 Enterobacterales and 42/109 P. aeruginosa isolates, explaining their resistant phenotype. Resistant isolates that yielded a negative qPCR result for any of the MBL encoding genes were subjected to WGS. The WGS analysis of the 67 remaining P. aeruginosa isolates showed mutations in genes previously associated with reduced susceptibility to CZA, such as those involved in the MexAB-OprM efflux pump and AmpC (PDC) hyperproduction, PoxB (blaOXA-50-like), FtsI (PBP3), DacB (PBP4), and OprD. The results presented here offer a snapshot of the molecular epidemiological landscape for CZA resistance before the introduction of this antibiotic into the Latin American market. Therefore, these results serve as a valuable comparison tool to trace the evolution of the resistance to CZA in this carbapenemase-endemic geographical region. IMPORTANCE In this manuscript, we determine the molecular mechanisms of ceftazidime-avibactam resistance in Enterobacterales and P. aeruginosa isolates from five Latin American countries. Our results reveal a low rate of resistance to ceftazidime-avibactam among Enterobacterales; in contrast, resistance in P. aeruginosa has proven to be more complex, as it might involve multiple known and possibly unknown resistance mechanisms.

Identification of mcr-1 Genes and Characterization of Resistance Mechanisms to Colistin in Escherichia coli Isolates from Colombian Hospitals.

We report the presence of the mcr-1 gene among 880 Escherichia coli clinical isolates collected in 13 hospitals from 12 Colombian cities between 2016 and 2019. Seven (0.8%) isolates were colistin resistant (MIC ≥ 4 µg/mL). These colistin-resistant isolates were screened for the presence of the mcr-1 gene; five carried the gene. These five isolates were subjected to whole genome sequencing (WGS) to identify additional resistomes and their ST. In addition, antimicrobial susceptibility testing revealed that all E. coli isolates carrying mcr-1 were susceptible to third generation-cephalosporin and carbapenems, except one, which carried an extended-spectrum ß-lactamase (CTX-M-55), along with the fosfomycin resistance encoding gene, fosA. WGS indicated that these isolates belonged to four distinct sequence types (ST58, ST46, ST393, and a newly described ST14315) and to phylogroups B1, A, and D. In this geographic region, the spread of mcr-1 in E. coli is low and has not been inserted into high-risk clones such as ST131, which has been present in the country longer.

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

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

Novel Insights into the Classification of Staphylococcal ß-Lactamases in Relation to the Cefazolin Inoculum Effect.

Cefazolin has become a prominent therapy for methicillin-susceptible Staphylococcus aureus (MSSA) infections. However, an important concern is the cefazolin inoculum effect (CzIE), a phenomenon mediated by staphylococcal ß-lactamases. Four variants of staphylococcal ß-lactamases have been described based on serological methodologies and limited sequence information. Here, we sought to reassess the classification of staphylococcal ß-lactamases and their correlation with the CzIE. We included a large collection of 690 contemporary bloodstream MSSA isolates recovered from Latin America, a region with a high prevalence of the CzIE. We determined cefazolin MICs at standard and high inoculums by broth microdilution. Whole-genome sequencing was performed to classify the ß-lactamase in each isolate based on the predicted full sequence of BlaZ. We used the classical schemes for ß-lactamase classification and compared it to BlaZ allotypes found in unique sequences using the genomic information. Phylogenetic analyses were performed based on the BlaZ and core-genome sequences. The overall prevalence of the CzIE was 40%. Among 641 genomes, type C was the most predominant ß-lactamase (37%), followed by type A (33%). We found 29 allotypes and 43 different substitutions in BlaZ. A single allotype, designated BlaZ-2, showed a robust and statistically significant association with the CzIE. Two other allotypes (BlaZ-3 and BlaZ-5) were associated with a lack of the CzIE. Three amino acid substitutions (A9V, E112A, and G145E) showed statistically significant association with the CzIE (P = <0.01). CC30 was the predominant clone among isolates displaying the CzIE. Thus, we provide a novel approach to the classification of the staphylococcal ß-lactamases with the potential to more accurately identify MSSA strains exhibiting the CzIE.