MUNITA SEPULVEDA, JOSE MANUEL

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MUNITA SEPULVEDA, JOSE MANUEL
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Email
josemunita@udd.cl
ORCID
0000-0002-7870-1056
Scopus Author ID
24825037700
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    P-186. Trends in Antimicrobial Resistance Among Adults Across 6 Hospitals in Argentina, Brazil, and Chile, 2018-2022
    (Oxford University Press (OUP), 2025-01-29)
    Siza, Charlene R
    ;
    Mahon, Garrett W
    ;
    Patel, Twisha S
    ;
    Garzon, Maria I
    ;
    Boszczowski, Icaro
    Background In 2019, an estimated 1.27 million deaths were attributed to bacterial antimicrobial resistance (AR) globally. During the Coronavirus Disease 2019 (COVID-19) Pandemic, additional strain was placed on healthcare systems that may have led to further increases in AR. We evaluated AR prevalence before and after the onset of COVID-19 in 6 healthcare facilities (HCF) in South America. Methods We conducted an ecological evaluation of HCF-wide AR prevalence in 4 private and 2 public HCFs in Argentina, Brazil, and Chile; 2 HCFs per country. We calculated percentage of non-susceptible (NS) or resistant (R) to select antibiotics among clinical isolates of Acinetobacter baumannii, Pseudomonas aeruginosa, Enterococcus spp., and Enterobacterales cultured from adult acute care inpatients. We compared percentage-NS or -R between the periods pre- (March 2018–February 2020) and post- (March 2020–February 2022) onset of the COVID-19 pandemic. Chi-square or Fisher’s exact tests were used with statistical significance set at a two-tailed p< 0.05. Results When comparing 2020-2022 to 2018-2020, 2/6 hospitals showed statistically significant increases (+14.1–19.2%) in carbapenem-NS A. baumannii. For carbapenem-NS P. aeruginosa, 1/6 hospitals showed a significant increase (+76.6%) and 1/6 showed a significant decrease (-52.4%). For carbapenem-NS Enterobacterales, 2/6 hospitals had significant increases (+50.7–236.2%) and 1 exhibited a significant decrease (-91.7%). For vancomycin-R Enterococcus spp., 2/6 hospitals had significant increases (+43.9–400.0%) and 2/6 hospitals had significant decreases (-49.0-60.7%). For Enterobacterales-R to 3rd generation cephalosporins, 2/6 hospitals showed significant increases (+16.0–110.9%) and 1/6 hospitals had a significant decrease (-40.4%) (Table). Conclusion Among the isolates from our study hospitals, we noted not only significant increases but also significant decreases across multiple AR profiles associated with multi-drug resistance. These data suggest that the pandemic may have led to changes in resistance among both gram-negative and gram-positive bacteria. Given the variability in these changes, further evaluation of infection rates would be valuable to confirm these findings. Disclosures José M Munita, MD, MSD: Grant/Research Support|Pfizer: Grant/Research Support
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    P-175. Assessing the Dynamics of Fecal Colonization with Antibiotic-Resistant Bacteria in a Chilean Cohort: A Longitudinal Study
    (Oxford University Press (OUP), 2025-01-29)
    Rafael, Araos
    ;
    Jara, Alejandro
    ;
    Sanchez, Felipe
    ;
    Adell, Aiko
    ;
    Olivares, Jorge
    Background In low- and middle-income countries, the community burden of antibiotic-resistant Gram-negative bacteria (AR-GNB) colonization is high. Understanding factors influencing AR-GNB colonization is crucial for controlling antimicrobial resistance. Methods We conducted a cohort study from December 2019 to November 2020 with community-dwelling adults in Molina, an agricultural town in Central Chile. We collected questionnaires and fecal samples every two weeks for six months to identify colonization by extended-spectrum cephalosporin-resistant Enterobacterales (ESCRE). ESCRE detection involved selective media screening, MALDI-TOF identification, and disk-diffusion antibiotic-susceptibility testing. We assessed the impact of epidemiological and clinical features and exposure to various water sources, foods, and animals on i) baseline ESCRE fecal colonization, ii) ESCRE acquisition during follow-up, and iii) ESCRE clearance. The study included 198 subjects, using multiple imputations for missing predictor values. We used two hidden Markov models for each dataset, with Model 1 assuming perfect sensitivity and specificity and Model 2 estimating sensitivity. A Bayesian approach with Markov chain Monte Carlo algorithms estimated odds ratios (OR) and credible intervals (CI). Results The sample consisted of 198 residents with a mean age of 60.9 and a predominance of women (75%). Model 1 showed that treating drinking water before consumption reduced the risk of baseline ESCRE colonization (OR: 0.38; 95% CI: 0.02 – 0.89). No significant associations were found for ESCRE acquisition during follow-up. Males and individuals with comorbidities had a lower risk of clearing ESCRE (ORs: 0.58, 0.54; CIs: 0.24 – 0.97, 0.258 – 0.88, respectively). Model 2, with imperfect sensitivity, showed similar results. Conclusion This study highlights the significance of environmental and individual health factors in ESCRE colonization. Interventions like treating drinking water could reduce baseline ESCRE colonization risk. The varied impacts of gender and comorbidities on ESCRE clearance provide insights for targeted AR-GNB management strategies. Further research is needed to understand these associations and develop effective community-level interventions against AMR. Disclosures All Authors: No reported disclosures
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    P-2214. The Microbiome of Community-Dwelling Adults and Risk Factors for Colonization with Antibiotic-Resistant Bacteria in Chile
    (Oxford University Press (OUP), 2025-01-29)
    Rafael, Araos
    ;
    Ugalde, Juan
    ;
    Jara, Alejandro
    ;
    Sanchez, Felipe
    ;
    RIVAS JIMENEZ, LINA MARIA  
    Background Intestinal colonization due to antibiotic-resistant bacteria (ARB) often precedes episodes of infection and fosters the spread of antibiotic resistance. This study explores the clinical, epidemiological, and microbiome factors associated with ARB colonization in Chilean adults. Methods A cross-sectional study of 357 community-dwelling individuals from a community in central Chile was conducted between December 2018 - May 2019, using stool samples and health questionnaires. Stool samples were cultured on selective media, followed by identification with MALDI-TOF and disc diffusion susceptibility method. Fecal microbiome assessments were conducted using 16S rRNA gene sequencing performed on Illumina MiSeq. ARB colonization was defined as phenotypic resistance of recovered isolates to extended-spectrum cephalosporins, fluoroquinolones, and/or carbapenems. Associations between colonization and clinical and epidemiological factors were analyzed through classification trees and logistic regression, while diversity and composition of microbiomes were compared between participants based on colonization status. Results No exposures were associated with the risk of ARB colonization. The microbiomes of colonized individuals featured Firmicutes, with Bacteroidetes, Actinobacteria, and Proteobacteria also present, paralleling the microbiome profile of the non-colonized individuals. However, ARB-colonized individuals had an overrepresentation of Escherichia/Shigella, Klebsiella, and Enterococcus genera. There were no differences in alpha or beta diversity by ARB colonization status. Conclusion The lack of risk factors regarding ARB colonization suggests that such colonization might occur without overt selective pressures. However, the overrepresentation of specific genera in colonized individuals could subtly indicate the influence of unrecognized selective pressures, such as environmental exposure to antibiotic residues. This scenario underscores the complexity of ARB dynamics and the need for further studies to explore potential environmental and indirect factors contributing to ARB colonization in the community setting. Disclosures All Authors: No reported disclosures
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    P-310. Evolutionary dynamics of the Chilean-Cordobes MRSA clone allowed the emergence of new MRSA clones in Chile
    (Oxford University Press (OUP), 2025-01-29)
    MartĂ­nez, Jose R W
    ;
    Campbell, Amy
    ;
    SPENCER SANDINO, MARIA DE LOS ANGELES  
    ;
    RIVAS JIMENEZ, LINA MARIA  
    ;
    DIAZ ORTIZ, SANDRA LORENA  
    Background The global spread of methicillin-resistant Staphylococcus aureus (MRSA) is associated with distinct clones predominating in specific geographical regions. Available evidence suggests that the Chilean-Cordobes clone (ChC), an ST5-SCCmecI lineage, has predominated in Chilean hospitals ever since its first description in 1998. However, we recently reported a gradual decrease in this lineage over time, with frequencies dropping from 94% (2000) to 52% (2016). To understand this clonal replacement event, we aimed to reconstruct the genomic evolution of the ChC in Latin America. Characterization of clades and sub-lineages of the ChC clone.Figure 1.Characterization of clades and sub-lineages of the ChC clone. A) Maximum clade credibility molecular clock analysis of the 596 MRSA genomes. A Bayesian molecular clock analysis was performed with BEAST using the isolation date of each genome as calibrator. The vertical lines show the scale of years. The colored strip showed the country of origin. The dots show the presence of mecA genotypes, heavy metal resistance genes (HMRGs), and SNPs in Sau1. The branches are colored based on the sub-lineage identification: ChC-I (magenta), ChC-II (orange), and ChC-III (green). B) Characterization of the ChC clades. The presence of each genetic element considered to characterize the clades are marked by a + symbol. C) Relative frequency of the ChC sub-lineages in Chile over time. The colored bars represent the relative frequency of each sub-lineage: ChC-I (magenta), ChC-II (orange), ChC-III (green), and unclassified (gray). Methods A total of 596 ChC MRSA isolates obtained from 6 Latin American countries between 1999-2018 were whole-genome sequenced and characterized using a Bayesian molecular clock analysis (MCA). Sub-lineages (SLs) observed in major divergence events were further characterized. Additionally, the frequency of each SL observed in our 1999-2018 collection was assessed in an independent group of genomes from 274 Chilean clinical MRSA isolates collected in 2022. Results Our MCA of ChC MRSA revealed 3 clades strongly related with different genomic traits, including: i) mecA genotype, ii) heavy metal resistance genes (HMRGs), and iii) changes in the Sau1 restriction-modification system (Sau1) (Fig. 1A). Each clade was classified as sub-lineage: ChC-I, ChC-II, and ChC-III (Fig. 1B). All the genomes from Argentina, Colombia, and Venezuela – countries where ChC was largely replaced - belonged to the ChC-II SL and harbored a Sau1 mutation (Fig. 1A). On the other hand, genomes obtained from Chile distributed in different SLs and exhibited a dynamic interchange over time (Fig. 1C). While between 1999-2003 most of the genomes belonged to SLs ChC-I and ChC-II, both SLs virtually disappeared in 2013-2018, period were >90% ChC genomes corresponded to ChC-III (Fig. 1C). In 2022, a majority of ChC MRSA had genomic features compatible with the ChC-III SL (Fig. 1C). Finally, the MCA revealed an evolutionary event within ChC-III dated in 2005, which was accompanied by the loss of HMRGs (Fig. 1A) Conclusion We describe the time evolution of several ChC clades, giving rise to sub-lineages that seem to play a role in the loss of dominance of the ChC MRSA clone in Chile and a consequent change in its epidemiology in the country. Disclosures José M Munita, MD, MSD: Grant/Research Support|Pfizer: Grant/Research Support
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    P-889. Therapeutic Failures of High Inoculum Infections with Cefazolin: Role of A Rapid Test and Prevalence of the Cefazolin Inoculum Effect in Methicillin-Susceptible <i>Staphylococcus aureus</i> (MSSA) Bloodstream Infections
    (Oxford University Press (OUP), 2025-01-29)
    Flores, Erika
    ;
    Dziadula, Jacob
    ;
    Panesso, Diana
    ;
    Singh, Kavindra
    ;
    Carvajal, Lina Paola
    Background Cefazolin (CFZ) remains a key therapy for MSSA bloodstream infections (BSIs), yet some studies suggest poorer outcomes when CFZ is used in the presence of cefazolin inoculum effect (CzIE). We developed a rapid colorimetric test with nitrocefin to detect CzIE in MSSA. Here, we report the performance of the rapid test in four recurrent BSIs caused by MSSA exhibiting the CzIE. Furthermore, we assess the local prevalence of CzIE using both standard broth microdilution (BMD) and the rapid test. Methods A chart review collected clinical data from four patients, including demographics, microbiologic features, antibiotic therapies, and clinical outcome. Patients were selected based on positive MSSA BSI after initial clearance, and availability of their index isolate. The nitrocefin-based rapid test was performed according to a published protocol. For the surveillance step, MSSA were collected from initial cultures of adult patients diagnosed with BSIs between July 2023 and April 2024 from 8 hospitals. The CzIE was assessed using BMD at standard (105) and high (107) inocula, with a cutoff CFZ MIC ≥ 16 μg/ml. The rapid test was performed in all isolates. Results All four patients had deep-seated infections, including endocarditis, osteomyelitis, or device-related infections, with two patients undergoing surgical interventions. While receiving CFZ therapy, all patients successfully cleared their MSSA BSI. After initial clearance, these patients received prolonged antibiotic therapy lasting ≥ 6 weeks, with 3 of 4 patients continuing with CFZ, as part of their initial therapy. Despite this, MSSA BSI recurred between 34 and 155 days after initial hospitalization. Notably, all index isolates tested positive for CzIE via the rapid test. During the surveillance period, we collected 196 isolates, with a 40% (79/196) prevalence of the CzIE based on BMD. The rapid nitrocefin test correctly identified 72 of 79 strains exhibiting the CzIE, with 91% sensitivity and 80.3% specificity. Conclusion These findings underscore a high prevalence of MSSA isolates exhibiting CzIE in BSIs. Patients infected with MSSA displaying CzIE may face an increased risk for recurrence when treated with CFZ. Further validation of these observations is warranted to better understand their clinical implications. Disclosures José M Munita, MD, MSD: Grant/Research Support|Pfizer: Grant/Research Support William R. Miller, M.D., Merck: Grant/Research Support|UptoDate: Royalties
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