RIVAS JIMENEZ, LINA MARIA
Thumbnail Image
Preferred name
RIVAS JIMENEZ, LINA MARIA
Main Affiliation
Email
lrivas@udd.cl
ORCID
Scopus Author ID
55921716700

Research Output

2024 2024 2023 2023 2022 2022 2021 2021 0.0 0.0 0.2 0.2 0.4 0.4 0.6 0.6 0.8 0.8 1.0 1.0 1.2 1.2 1.4 1.4 1.6 1.6 1.8 1.8 2.0 2.0

Filters

4
Reset filters

Settings
Now showing 1 - 4 of 4
No Thumbnail Available
Publication

Role of the multi-drug efflux systems on the baseline susceptibility to ceftazidime/avibactam and ceftolozane/tazobactam in clinical isolates of non-carbapenemase-producing carbapenem-resistant Pseudomonas aeruginosa

2022 , María José Contreras-Gómez , José R. W. Martinez , RIVAS JIMENEZ, LINA MARIA , Juan A. Ugalde , Roberto Riquelme-Neira , Aniela Wozniak , Patricia García , Jorge Olivares-Pacheco , MUNITA SEPULVEDA, JOSE MANUEL , ALCALDE RICO, MANUEL

Carbapenem-resistant Pseudomonas aeruginosa (CRPA) is one of the pathogens that urgently needs new drugs and new alternatives for its control. The primary strategy to combat this bacterium is combining treatments of beta-lactam with a beta-lactamase inhibitor. The most used combinations against P. aeruginosa are ceftazidime/avibactam (CZA) and ceftolozane/tazobactam (C/T). Although mechanisms leading to CZA and C/T resistance have already been described, among which are the resistance-nodulation-division (RND) efflux pumps, the role that these extrusion systems may play in CZA, and C/T baseline susceptibility of clinical isolates remains unknown. For this purpose, 161 isolates of non-carbapenemase-producing (Non-CP) CRPA were selected, and susceptibility tests to CZA and C/T were performed in the presence and absence of the RND efflux pumps inhibitor, Phenylalanine-arginine β-naphthylamide (PAβN). In the absence of PAβN, C/T showed markedly higher activity against Non-CP-CRPA isolates than observed for CZA. These results were even more evident in isolates classified as extremely-drug resistant (XDR) or with difficult-to-treat resistance (DTR), where CZA decreased its activity up to 55.2% and 20.0%, respectively, whereas C/T did it up to 82.8% (XDR), and 73.3% (DTR). The presence of PAβN showed an increase in both CZA (37.6%) and C/T (44.6%) activity, and 25.5% of Non-CP-CRPA isolates increased their susceptibility to these two combined antibiotics. However, statistical analysis showed that only the C/T susceptibility of Non-CP-CRPA isolates was significantly increased. Although the contribution of RND activity to CZA and C/T baseline susceptibility was generally low (two-fold decrease of minimal inhibitory concentrations [MIC]), a more evident contribution was observed in a non-minor proportion of the Non-CP-CRPA isolates affected by PAβN [CZA: 25.4% (15/59); C/T: 30% (21/70)]. These isolates presented significantly higher MIC values for C/T. Therefore, we conclude that RND efflux pumps are participating in the phenomenon of baseline susceptibility to CZA and, even more, to C/T. However, the genomic diversity of clinical isolates is so great that deeper analyzes are necessary to determine which elements are directly involved in this phenomenon.

View
No Thumbnail Available
Publication

A multispecies outbreak of carbapenem-resistant bacteria harboring the blaKPC gene in a non-classical transposon element

2021 , Aniela Wozniak , Cristian Figueroa , Francisco Moya-Flores , Piero Guggiana , Claudia Castillo , RIVAS JIMENEZ, LINA MARIA , Patricia C. García , MUNITA SEPULVEDA, JOSE MANUEL

Abstract Background Klebsiella pneumoniae is the most frequent KPC-producing bacteria. The blaKPC gene is frequently embedded in Tn4401 transposon, and less frequently in non-Tn4401 elements (NTEKPC) variants I-III. The first case of KPC in the UC-CHRISTUS Clinical Hospital was detected in Pseudomonas aeruginosa. Soon after this event, KPC was detected in 2 additional Pseudomonas aeruginosa, 3 Escherichia coli, 3 Enterobacter cloacae, 3 Klebsiella pneumoniae, and 1 Citrobacter freundii, isolated from 6 different patients. We aimed to elucidate the possible mechanisms of genetic transfer and dissemination of the blaKPC gene among isolates of this multispecies outbreak. A molecular epidemiology analysis of the above mentioned clinical isolates (n = 13) through Multi-Locus Sequence Typing, plasmid analysis, Pulsed-Field Gel-Electrophoresis, and Whole-genome sequencing (WGS) was performed. Results High-risk sequence types were found: K. pneumoniae ST11, P. aeruginosa ST654, and E. cloacae ST114. All enterobacterial isolates were not clonal except for 3 E. coli isolated from the same patient. WGS analysis in 6 enterobacterial isolates showed that 4 of them had blaKPC embedded in a novel variant of NTEKPC designated NTEKPC-IIe. Upstream of blaKPC gene there was a 570 pb truncated blaTEM-1 gene followed by an insertion sequence that was 84% similar to ISEc63, a 4473 bp element of the Tn3 family. Downstream the blaKPC gene there was a truncated ISKpn6 gene, and the inverted repeat right sequence of Tn4401. The ISec63-like element together with the blaKPC gene plus Tn4401 remnants were inserted in the Tra operon involved in conjugative transfer of the plasmid. This NTE was carried in a broad host-range IncN plasmid. P. aeruginosa isolates carried blaKPC gene embedded in a typical Tn4401b transposon in a different plasmid, suggesting that there was no plasmid transfer between Enterobacteriaceae and P. aeruginosa as initially hypothesized. Conclusions Most enterobacterial isolates had blaKPC embedded in the same NTEKPC-IIe element, suggesting that this multispecies KPC outbreak was due to horizontal gene transfer rather than clonal spread. This poses a greater challenge to infection control measures often directed against containment of clonal spread.

View
No Thumbnail Available
Publication

Ceftazidime/avibactam resistance is associated with PER-3-producing ST309 lineage in Chilean clinical isolates of non-carbapenemase producing Pseudomonas aeruginosa

2024 , Katherine D. Soto , ALCALDE RICO, MANUEL , UGALDE, JUAN ANTONIO , Jorge Olivares Pacheco , Valeria Quiroz , Bárbara Brito , RIVAS JIMENEZ, LINA MARIA , MUNITA SEPULVEDA, JOSE MANUEL , GARCÍA CEBALLOS, PATRICIA , Aniela Wozniak

IntroductionCeftazidime/avibactam (CZA) is indicated against multidrug-resistant Pseudomonas aeruginosa, particularly those that are carbapenem resistant. CZA resistance in P. aeruginosa producing PER, a class A extended-spectrum β-lactamase, has been well documented in vitro. However, data regarding clinical isolates are scarce. Our aim was to analyze the contribution of PER to CZA resistance in non-carbapenemase-producing P. aeruginosa clinical isolates that were ceftazidime and/or carbapenem non-susceptible.MethodsAntimicrobial susceptibility was determined through agar dilution and broth microdilution, while blaPER gene was screened through PCR. All PER-positive isolates and five PER-negative isolates were analyzed through Whole Genome Sequencing. The mutational resistome associated to CZA resistance was determined through sequence analysis of genes coding for PBPs 1b, 3 and 4, MexAB-OprM regulators MexZ, MexR, NalC and NalD, AmpC regulators AmpD and AmpR, and OprD porin. Loss of blaPER-3 gene was induced in a PER-positive isolate by successive passages at 43°C without antibiotics. ResultsTwenty-six of 287 isolates studied (9.1%) were CZA-resistant. Thirteen of 26 CZA-resistant isolates (50%) carried blaPER. One isolate carried blaPER but was CZA-susceptible. PER-producing isolates had significantly higher MICs for CZA, amikacin, gentamicin, ceftazidime, meropenem and ciprofloxacin than non-PER-producing isolates. All PER-producing isolates were ST309 and their blaPER-3 gene was associated to ISCR1, an insertion sequence known to mobilize adjacent DNA. PER-negative isolates were classified as ST41, ST235 (two isolates), ST395 and ST253. PER-negative isolates carried genes for narrow-spectrum β-lactamases and the mutational resistome showed that all isolates had one major alteration in at least one of the genes analyzed. Loss of blaPER-3 gene restored susceptibility to CZA, ceftolozane/tazobactam and other β-lactamsin the in vitro evolved isolate. DiscussionPER-3-producing ST309 P. aeruginosa is a successful multidrug-resistant clone with blaPER-3 gene implicated in resistance to CZA and other β-lactams.

View
No Thumbnail Available
Publication

Real-World Performance of Susceptibility Testing for Ceftolozane/Tazobactam against Non-Carbapenemase-Producing Carbapenem-Resistant Pseudomonas aeruginosa

2022 , RIVAS JIMENEZ, LINA MARIA , Manuel Alcalde-Rico , José R. W. Martínez , María Victoria Moreno , Pamela Rojas , Aniela Wozniak , Patricia García , Jorge Olivares-Pacheco , William R. Miller , Cesar A. Arias , Ayesha Khan , MUNITA SEPULVEDA, JOSE MANUEL

Ceftolozane/tazbactam (C/T) is a potent anti-pseudomonal agent that has clinical utility against infections caused by non-carbapenemase, producing-carbapenem-resistant Pseudomonas aeruginosa (non-CP-CR-PA). Accurate, precise, and reliable antimicrobial susceptibility testing (AST) is crucial to guide clinical decisions.

View